NM_000283.4(PDE6B):c.1604T>A (p.Ile535Asn) AND Retinitis pigmentosa 40

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 22, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV002250571.1

Allele description [Variation Report for NM_000283.4(PDE6B):c.1604T>A (p.Ile535Asn)]

NM_000283.4(PDE6B):c.1604T>A (p.Ile535Asn)

Gene:

PDE6B:phosphodiesterase 6B [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4p16.3

Genomic location:

Preferred name:

NM_000283.4(PDE6B):c.1604T>A (p.Ile535Asn)

HGVS:

NC_000004.12:g.660603T>A
NG_009839.1:g.40030T>A
NM_000283.4:c.1604T>AMANE SELECT
NM_001145291.2:c.1604T>A
NM_001145292.2:c.767T>A
NM_001350154.3:c.767T>A
NM_001350155.3:c.449T>A
NM_001379246.1:c.767T>A
NM_001379247.1:c.767T>A
NP_000274.2:p.Ile535Asn
NP_000274.3:p.Ile535Asn
NP_001138763.2:p.Ile535Asn
NP_001138764.2:p.Ile256Asn
NP_001337083.1:p.Ile256Asn
NP_001337084.1:p.Ile150Asn
NP_001366175.1:p.Ile256Asn
NP_001366176.1:p.Ile256Asn
NC_000004.11:g.654392T>A
NM_000283.3:c.1604T>A
P35913:p.Ile535Asn

Protein change:

I150N

Links:

UniProtKB: P35913#VAR_009291; dbSNP: rs527236088

NCBI 1000 Genomes Browser:

rs527236088

Molecular consequence:

NM_000283.4:c.1604T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001145291.2:c.1604T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001145292.2:c.767T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001350154.3:c.767T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001350155.3:c.449T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001379246.1:c.767T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001379247.1:c.767T>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Retinitis pigmentosa 40 (RP40)
Identifiers:: MONDO: MONDO:0013429; MedGen: C3151107; Orphanet: 791; OMIM: 613801

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002521834	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (May 22, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 9543643, 26155838, 25827439, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002521834

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(May 22, 2022)

germline

clinical testing

PubMed (4)
[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	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

A novel homozygous Ile535Asn mutation in the rod cGMP phosphodiesterase beta-subunit gene in two brothers of a Japanese family with autosomal recessive retinitis pigmentosa.

Saga M, Mashima Y, Akeo K, Kudoh J, Oguchi Y, Shimizu N.

Curr Eye Res. 1998 Mar;17(3):332-5.

PubMed [citation]

PMID:: 9543643

The diagnostic application of targeted re-sequencing in Korean patients with retinitis pigmentosa.

Yoon CK, Kim NK, Joung JG, Shin JY, Park JH, Eum HH, Lee HO, Park WY, Yu HG.

BMC Genomics. 2015 Jul 9;16:515. doi: 10.1186/s12864-015-1723-x.

PubMed [citation]

PMID:: 26155838
PMCID:: PMC4496857

See all PubMed Citations (4)

Details of each submission

From 3billion, SCV002521834.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (4)

Description

The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: <0.001%). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.82; 3Cnet: 3CNET). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with PDE6B related disorder (ClinVar ID: VCV000143067 / PMID: 9543643 / 3billion dataset). The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least one similarly affected unrelated individual (PMID: 25827439, 26155838) and to co-segregate with the disease in at least one similarly affected relative/individual in the same family or similarly affected unrelated family (PMID:25827439). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.

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

Last Updated: Jun 23, 2024

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