NM_001080442.3(SLC38A8):c.848A>C (p.Asp283Ala) AND Foveal hypoplasia - optic nerve decussation defect - anterior segment dysgenesis syndrome - ClinVar

NM_001080442.3(SLC38A8):c.848A>C (p.Asp283Ala) AND Foveal hypoplasia - optic nerve decussation defect - anterior segment dysgenesis syndrome

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Jun 2, 2023
Review status:: criteria provided, conflicting classifications

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:: RCV000991179.5

Allele description [Variation Report for NM_001080442.3(SLC38A8):c.848A>C (p.Asp283Ala)]

NM_001080442.3(SLC38A8):c.848A>C (p.Asp283Ala)

Gene:

SLC38A8:solute carrier family 38 member 8 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16q23.3

Genomic location:

Preferred name:

NM_001080442.3(SLC38A8):c.848A>C (p.Asp283Ala)

HGVS:

NC_000016.10:g.84017245T>G
NG_034136.1:g.29913A>C
NM_001080442.3:c.848A>CMANE SELECT
NP_001073911.1:p.Asp283Ala
NP_001073911.1:p.Asp283Ala
NC_000016.9:g.84050850T>G
NM_001080442.1:c.848A>C
NM_001080442.2:c.848A>C
p.Asp283Ala

Protein change:

D283A

Links:

dbSNP: rs139373929

NCBI 1000 Genomes Browser:

rs139373929

Molecular consequence:

NM_001080442.3:c.848A>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Foveal hypoplasia - optic nerve decussation defect - anterior segment dysgenesis syndrome
Synonyms:: Foveal hypoplasia 2; FOVEAL HYPOPLASIA 2 WITH OR WITHOUT OPTIC NERVE MISROUTING AND/OR ANTERIOR SEGMENT DYSGENESIS; FOVEAL HYPOPLASIA 2 WITH OR WITHOUT MICROPHTHALMIA OR COLOBOMA; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0012216; MedGen: C3807873; Orphanet: 397618; OMIM: 609218

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001142464	Reproductive Health Research and Development, BGI Genomics	no assertion criteria provided	Uncertain significance (Jan 6, 2020)	germline	curation
SCV001432155	Undiagnosed Diseases Network, NIH - Undiagnosed Diseases Network (NIH), UDN	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 8, 2020)	paternal	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004238665	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jun 2, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001142464

Reproductive Health Research and Development, BGI Genomics

no assertion criteria provided

Uncertain significance
(Jan 6, 2020)

germline

curation

SCV001432155

Undiagnosed Diseases Network, NIH - Undiagnosed Diseases Network (NIH), UDN

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Apr 8, 2020)

paternal

clinical testing

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

SCV004238665

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jun 2, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing, curation
Causasians	paternal	yes	1	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Reproductive Health Research and Development, BGI Genomics, SCV001142464.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	not provided

Description

NM_001080442.1:c.848A>C in the SLC38A8 gene has an allele frequency of 0.006 in Ashkenazi Jewish subpopulation in the gnomAD database. Pathogenic computational verdict because pathogenic predictions from DANN, EIGEN, FATHMM-MKL, M-CAP, MutationAssessor, MutationTaster, PrimateAI, REVEL and SIFT. We interpret it as variant of uncertain significance (VUS). ACMG/AMP criteria applied: PP3.

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

From Undiagnosed Diseases Network, NIH - Undiagnosed Diseases Network (NIH), UDN, SCV001432155.1

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

Description

This variant was observed in a patient with foveal hypoplasia and a second likely pathogenic variant.

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

From Revvity Omics, Revvity, SCV004238665.1

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

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

Last Updated: Sep 29, 2024

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