NM_000441.2(SLC26A4):c.1001+1G>T AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Apr 3, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000728208.11

Allele description [Variation Report for NM_000441.2(SLC26A4):c.1001+1G>T]

NM_000441.2(SLC26A4):c.1001+1G>T

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.1001+1G>T

HGVS:

NC_000007.14:g.107683538G>T
NG_008489.1:g.27904G>T
NM_000441.2:c.1001+1G>TMANE SELECT
NC_000007.13:g.107323983G>T
NM_000441.1:c.1001+1G>T

Links:

dbSNP: rs80338849

NCBI 1000 Genomes Browser:

rs80338849

Molecular consequence:

NM_000441.2:c.1001+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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txid451320[Organism:noexp] (0)
PMC
Homo sapiens isolate CHM13 chromosome 19, alternate assembly T2T-CHM13v2.0
Homo sapiens isolate CHM13 chromosome 19, alternate assembly T2T-CHM13v2.0
gi|2194972797|gnl|ASM:GCF_009914825 ef|NC_060943.1||gpp|GPC_000012758.1||gnl|NCBI_GENOMES|119579

Nucleotide
Gene Links for GEO Profiles (Select 53509349) (2)
Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000855752	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (Aug 8, 2017)	germline	clinical testing	Citation Link,
SCV001385487	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 13, 2023)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 9618167, 18167283, 26744121, 16199547, 16283880, 25394566, 26252218, 26445815, 28492532
SCV002817947	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Apr 3, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000855752

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL Classification Definitions 2015)

Pathogenic
(Aug 8, 2017)

germline

clinical testing

Citation Link,

SCV001385487

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 13, 2023)

germline

clinical testing

PubMed (9)
[See all records that cite these PMIDs]

SCV002817947

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Apr 3, 2024)

germline

clinical testing

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Molecular analysis of the PDS gene in Pendred syndrome.

Coyle B, Reardon W, Herbrick JA, Tsui LC, Gausden E, Lee J, Coffey R, Grueters A, Grossman4 A, Phelps PD, Luxon L, Kendall-Taylor P, Scherer SW, Trembath RC.

Hum Mol Genet. 1998 Jul;7(7):1105-12.

PubMed [citation]

PMID:: 9618167

[Screening of SLC26A4 (PDS) gene mutation in cochlear implant recipients with inner ear malformation].

Chen DY, Chen XW, Jin X, Zuo J, Wei CG, Cao KL, Fang FD.

Zhonghua Yi Xue Za Zhi. 2007 Oct 30;87(40):2820-4. Chinese.

PubMed [citation]

PMID:: 18167283

See all PubMed Citations (9)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000855752.1

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001385487.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 370123). Disruption of this splice site has been observed in individuals with hearing loss (PMID: 9618167, 18167283, 26744121). This variant is present in population databases (rs80338849, gnomAD 0.01%). This sequence change affects a donor splice site in intron 8 of the SLC26A4 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SLC26A4 are known to be pathogenic (PMID: 16283880, 25394566, 26252218, 26445815).

#	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 GeneDx, SCV002817947.2

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

Description

Reported in association with hearing loss in published literature listed in the Human Gene Mutation Database, but the content of the publication is not available to GeneDx (PMID: 18167283); Canonical splice site variant predicted to result in a null allele in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 25525159, 18167283)

#	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: Oct 8, 2024

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