NM_005548.3(KARS1):c.433T>C (p.Tyr145His) AND Autosomal recessive nonsyndromic hearing loss 89

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 17, 2014
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000054525.7

Allele description [Variation Report for NM_005548.3(KARS1):c.433T>C (p.Tyr145His)]

NM_005548.3(KARS1):c.433T>C (p.Tyr145His)

Gene:

KARS1:lysyl-tRNA synthetase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16q23.1

Genomic location:

Preferred name:

NM_005548.3(KARS1):c.433T>C (p.Tyr145His)

HGVS:

NC_000016.10:g.75636503A>G
NG_028025.1:g.16185T>C
NM_001130089.2:c.517T>C
NM_001378148.1:c.-36T>C
NM_005548.3:c.433T>CMANE SELECT
NP_001123561.1:p.Tyr173His
NP_001123561.1:p.Tyr173His
NP_005539.1:p.Tyr145His
LRG_366t1:c.517T>C
LRG_366:g.16185T>C
LRG_366p1:p.Tyr173His
NC_000016.9:g.75670401A>G
NM_001130089.1:c.517T>C
p.(Tyr173His)

Protein change:

Y145H; TYR173HIS

Links:

OMIM: 601421.0003; dbSNP: rs397514745

NCBI 1000 Genomes Browser:

rs397514745

Molecular consequence:

NM_001378148.1:c.-36T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001130089.2:c.517T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_005548.3:c.433T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Autosomal recessive nonsyndromic hearing loss 89
Synonyms:: Deafness, autosomal recessive 89
Identifiers:: MONDO: MONDO:0013489; MedGen: C3151351; Orphanet: 90636; OMIM: 613916

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000083003	OMIM	no assertion criteria provided	Pathogenic (Jul 11, 2013)	germline	literature only	PubMed (1) [See all records that cite this PMID] Santos-Cortez, R. L. P., Lee, K., Azeem, Z., Antonellis, P. J., Pollock, L. M., Khan, S., Irfanullah, Andrade-Elizondo, P. B., Chiu, I., Adams, M. D., Basit, S., Smith, J. D., University of Washington Center for Mendelian Genomics, Nickerson, D. A., McDermott, B. M., Jr., Ahmad, W., Leal, S. M. Mutations in KARS, encoding lysyl-tRNA synthetase, cause autosomal-recessive nonsyndromic hearing impairment DFNB89. Am. J. Hum. Genet. 93: 132-140, 2013.,
SCV000249614	Department of Molecular and Human Genetics, Baylor College of Medicine See additional submitters University of Washington Center for Mendelian Genomics, University of Washington	no assertion criteria provided	Pathogenic (Jan 17, 2014)	germline	research	PubMed (2) [See all records that cite these PMIDs] 23768514, 24824130

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000083003

OMIM

no assertion criteria provided

Pathogenic
(Jul 11, 2013)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

Santos-Cortez, R. L. P., Lee, K., Azeem, Z., Antonellis, P. J., Pollock, L. M., Khan, S., Irfanullah, Andrade-Elizondo, P. B., Chiu, I., Adams, M. D., Basit, S., Smith, J. D., University of Washington Center for Mendelian Genomics, Nickerson, D. A., McDermott, B. M., Jr., Ahmad, W., Leal, S. M. Mutations in KARS, encoding lysyl-tRNA synthetase, cause autosomal-recessive nonsyndromic hearing impairment DFNB89. Am. J. Hum. Genet. 93: 132-140, 2013.,

SCV000249614

Department of Molecular and Human Genetics, Baylor College of Medicine

See additional submitters

no assertion criteria provided

Pathogenic
(Jan 17, 2014)

germline

research

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	research
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

DFNB89, a novel autosomal recessive nonsyndromic hearing impairment locus on chromosome 16q21-q23.2.

Basit S, Lee K, Habib R, Chen L, Umm-e-Kalsoom, Santos-Cortez RL, Azeem Z, Andrade P, Ansar M, Ahmad W, Leal SM.

Hum Genet. 2011 Apr;129(4):379-85. doi: 10.1007/s00439-010-0934-0. Epub 2010 Dec 22.

PubMed [citation]

PMID:: 21181198
PMCID:: PMC3312604

Mutations in KARS, encoding lysyl-tRNA synthetase, cause autosomal-recessive nonsyndromic hearing impairment DFNB89.

Santos-Cortez RL, Lee K, Azeem Z, Antonellis PJ, Pollock LM, Khan S, Irfanullah, Andrade-Elizondo PB, Chiu I, Adams MD, Basit S, Smith JD; University of Washington Center for Mendelian Genomics., Nickerson DA, McDermott BM Jr, Ahmad W, Leal SM.

Am J Hum Genet. 2013 Jul 11;93(1):132-40. doi: 10.1016/j.ajhg.2013.05.018. Epub 2013 Jun 13.

PubMed [citation]

PMID:: 23768514
PMCID:: PMC3710764

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000083003.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In affected individuals from 2 consanguineous Pakistani families with nonsyndromic deafness (DFNB89; 613916), 1 of which (family 4406) had previously been studied by Basit et al. (2011), Santos-Cortez et al. (2013) identified homozygosity for a c.517T-C transition in exon 5 of the KARS gene, resulting in a tyr173-to-his (Y173H) substitution at a highly conserved residue within the beta-2 strand. The mutation segregated with disease in both families and was not found in 325 ethnically matched controls or in variant databases.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Department of Molecular and Human Genetics, Baylor College of Medicine, SCV000249614.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (2)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Dec 24, 2023

ClinVar

Relating variation to medicine