NM_000441.2(SLC26A4):c.1069G>A (p.Ala357Thr) AND Pendred syndrome

Germline classification:: Benign (3 submissions)
Last evaluated:: Feb 25, 2019
Review status:: 3 stars out of maximum of 4 stars
reviewed by expert panel

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:: RCV000275313.7

Allele description [Variation Report for NM_000441.2(SLC26A4):c.1069G>A (p.Ala357Thr)]

NM_000441.2(SLC26A4):c.1069G>A (p.Ala357Thr)

Gene:

SLC26A4:solute carrier family 26 member 4 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q22.3

Genomic location:

Preferred name:

NM_000441.2(SLC26A4):c.1069G>A (p.Ala357Thr)

Other names:

NM_000441.1(SLC26A4):c.1069G>A

HGVS:

NC_000007.14:g.107689120G>A
NG_008489.1:g.33486G>A
NM_000441.2:c.1069G>AMANE SELECT
NP_000432.1:p.Ala357Thr
NC_000007.13:g.107329565G>A
NM_000441.1:c.1069G>A
c.1069G>A

Protein change:

A357T

Links:

dbSNP: rs145467740

NCBI 1000 Genomes Browser:

rs145467740

Molecular consequence:

NM_000441.2:c.1069G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Pendred syndrome (PDS)
Synonyms:: DEAFNESS WITH GOITER; HYPOTHYROIDISM, CONGENITAL, DUE TO DYSHORMONOGENESIS, 2B; THYROID DYSHORMONOGENESIS 2B; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010134; MedGen: C0271829; Orphanet: 705; OMIM: 274600

Recent activity

Clear Turn Off Turn On

hypothetical protein BRO16_14195 [Xanthomonas oryzae pv. oryzae]
hypothetical protein BRO16_14195 [Xanthomonas oryzae pv. oryzae]
gi|1419420329|gb|RBA57770.1||gnl|WG G|BRO16_14195

Protein
Generalized tetanus
Generalized tetanus

MedGen
C0343497[conceptid] (1)
MedGen

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
SCV000466097	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (Jan 13, 2018)	germline	clinical testing	Citation Link,
SCV000927023	ClinGen Hearing Loss Variant Curation Expert Panel	reviewed by expert panel (ClinGen HL ACMG Specifications v1)	Benign (Feb 25, 2019)	germline	curation	Citation Link,
SCV001459866	Natera, Inc.	no assertion criteria provided	Uncertain significance (Dec 16, 2019)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000466097

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Uncertain significance
(Jan 13, 2018)

germline

clinical testing

Citation Link,

SCV000927023

ClinGen Hearing Loss Variant Curation Expert Panel

reviewed by expert panel

(ClinGen HL ACMG Specifications v1)

Benign
(Feb 25, 2019)

germline

curation

Citation Link,

SCV001459866

Natera, Inc.

no assertion criteria provided

Uncertain significance
(Dec 16, 2019)

germline

clinical testing

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

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000466097.3

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

Description

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

#	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 ClinGen Hearing Loss Variant Curation Expert Panel, SCV000927023.1

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

Description

The filtering allele frequency of the p.Ala357Thr variant in the SLC26A4 gene is 0.47% for African chromosomes by gnomAD (136/24968 with 95% CI), which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal recessive Pendred syndrome variants (BA1). The REVEL computational prediction analysis tool produces a score of 0.849, which is above the threshold necessary to apply PP3; however, this information is not predictive of pathogenicity on its own and is not considered in conflict with evidence that supports a benign interpretation. In summary, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel: BA1.

#	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 Natera, Inc., SCV001459866.1

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

#	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: Oct 26, 2024

ClinVar

Relating variation to medicine