NM_000441.2(SLC26A4):c.1149+3A>G AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 17, 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:: RCV001574741.5

Allele description [Variation Report for NM_000441.2(SLC26A4):c.1149+3A>G]

NM_000441.2(SLC26A4):c.1149+3A>G

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.1149+3A>G

HGVS:

NC_000007.14:g.107689203A>G
NG_008489.1:g.33569A>G
NM_000441.2:c.1149+3A>GMANE SELECT
NC_000007.13:g.107329648A>G
NM_000441.1:c.1149+3A>G
c.1149+3A>G

Links:

dbSNP: rs111033314

NCBI 1000 Genomes Browser:

rs111033314

Molecular consequence:

NM_000441.2:c.1149+3A>G - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001801611	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jan 3, 2019)	germline	clinical testing	Citation Link,
SCV004295491	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 17, 2024)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 15679828, 28964290, 31387071, 34680964, 17576681, 9536098, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001801611

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Jan 3, 2019)

germline

clinical testing

Citation Link,

SCV004295491

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 17, 2024)

germline

clinical testing

PubMed (7)
[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	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Genetic basis of hearing loss associated with enlarged vestibular aqueducts in Koreans.

Park HJ, Lee SJ, Jin HS, Lee JO, Go SH, Jang HS, Moon SK, Lee SC, Chun YM, Lee HK, Choi JY, Jung SC, Griffith AJ, Koo SK.

Clin Genet. 2005 Feb;67(2):160-5.

PubMed [citation]

PMID:: 15679828

Novel pathogenic variants underlie SLC26A4-related hearing loss in a multiethnic cohort.

Cengiz FB, Yilmazer R, Olgun L, Sennaroglu L, Kirazli T, Alper H, Olgun Y, Incesulu A, Atik T, Huesca-Hernandez F, Domínguez-Aburto J, González-Rosado G, Hernandez-Zamora E, Arenas-Sordo ML, Menendez I, Orhan KS, Avci H, Mahdieh N, Bonyadi M, Foster J 2nd, Duman D, Ozkinay F, et al.

Int J Pediatr Otorhinolaryngol. 2017 Oct;101:167-171. doi: 10.1016/j.ijporl.2017.08.006. Epub 2017 Aug 8.

PubMed [citation]

PMID:: 28964290
PMCID:: PMC5679420

See all PubMed Citations (7)

Details of each submission

From GeneDx, SCV001801611.1

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

Description

Non-canonical splice site variant in a gene for which loss-of-function is a known mechanism of disease; functional studies confirm variant destroys the splice donor site of intron 9 and causes skipping of exon 9 (Park et al., 2005); This variant is associated with the following publications: (PMID: 31387071, 31033086, 15679828, 28964290, 24007330, 25488846, 25525159, 23469187)

#	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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004295491.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This sequence change falls in intron 9 of the SLC26A4 gene. It does not directly change the encoded amino acid sequence of the SLC26A4 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs111033314, gnomAD 0.01%). This variant has been observed in individual(s) with SLC26A4-related conditions (PMID: 15679828, 28964290, 31387071, 34680964). ClinVar contains an entry for this variant (Variation ID: 43493). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

#	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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