7-103412988-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_198999.3(SLC26A5):c.403+14T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 1,507,310 control chromosomes in the GnomAD database, including 65,021 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 14709 hom., cov: 31)

Exomes 𝑓: 0.26 ( 50312 hom. )

Consequence

SLC26A5
NM_198999.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.0920

Variant links:

Genes affected

SLC26A5 (HGNC:9359): (solute carrier family 26 member 5) This gene encodes a member of the SLC26A/SulP transporter family. The protein functions as a molecular motor in motile outer hair cells (OHCs) of the cochlea, inducing changes in cell length that act to amplify sound levels. The transmembrane protein is an incomplete anion transporter, and does not allow anions to cross the cell membrane but instead undergoes a conformational change in response to changes in intracellular Cl- levels that results in a change in cell length. The protein functions at microsecond rates, which is several orders of magnitude faster than conventional molecular motor proteins. Mutations in this gene are potential candidates for causing neurosensory deafness. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Nov 2009]

SLC26A5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 7-103412988-A-G is Benign according to our data. Variant chr7-103412988-A-G is described in ClinVar as [Benign]. Clinvar id is 48339.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-103412988-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A5	NM_198999.3 link	c.403+14T>C		intron_variant	Intron 5 of 19	ENST00000306312.8	NP_945350.1	P58743-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC26A5	ENST00000306312.8 link	c.403+14T>C	intron_variant	Intron 5 of 19	1	NM_198999.3	ENSP00000304783.3	P58743-1
SLC26A5	ENST00000393727.5 link	c.403+14T>C	intron_variant	Intron 3 of 17	1		ENSP00000377328.1	Q7Z7F4
SLC26A5	ENST00000393723.2 link	c.403+14T>C	intron_variant	Intron 3 of 16	1		ENSP00000377324.1	P58743-6

Frequencies

GnomAD3 genomes

AF:

0.382

AC:

58081

AN:

151920

Hom.:

14664

Cov.:

show subpopulations

Gnomad AFR

AF:

0.722

Gnomad AMI

AF:

0.152

Gnomad AMR

AF:

0.279

Gnomad ASJ

AF:

0.182

Gnomad EAS

AF:

0.403

Gnomad SAS

AF:

0.348

Gnomad FIN

AF:

0.315

Gnomad MID

AF:

0.194

Gnomad NFE

AF:

0.227

Gnomad OTH

AF:

0.304

GnomAD3 exomes

AF:

0.305

AC:

76450

AN:

250458

Hom.:

13934

AF XY:

0.296

AC XY:

40124

AN XY:

135396

show subpopulations

Gnomad AFR exome

AF:

0.739

Gnomad AMR exome

AF:

0.321

Gnomad ASJ exome

AF:

0.168

Gnomad EAS exome

AF:

0.410

Gnomad SAS exome

AF:

0.346

Gnomad FIN exome

AF:

0.306

Gnomad NFE exome

AF:

0.225

Gnomad OTH exome

AF:

0.252

GnomAD4 exome

AF:

0.256

AC:

347005

AN:

1355272

Hom.:

50312

Cov.:

AF XY:

0.257

AC XY:

174891

AN XY:

680444

show subpopulations

Gnomad4 AFR exome

AF:

0.743

Gnomad4 AMR exome

AF:

0.310

Gnomad4 ASJ exome

AF:

0.170

Gnomad4 EAS exome

AF:

0.392

Gnomad4 SAS exome

AF:

0.347

Gnomad4 FIN exome

AF:

0.302

Gnomad4 NFE exome

AF:

0.225

Gnomad4 OTH exome

AF:

0.273

GnomAD4 genome

AF:

0.383

AC:

58187

AN:

152038

Hom.:

14709

Cov.:

AF XY:

0.384

AC XY:

28524

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.722

Gnomad4 AMR

AF:

0.279

Gnomad4 ASJ

AF:

0.182

Gnomad4 EAS

AF:

0.403

Gnomad4 SAS

AF:

0.349

Gnomad4 FIN

AF:

0.315

Gnomad4 NFE

AF:

0.227

Gnomad4 OTH

AF:

0.305

Alfa

AF:

0.291

Hom.:

2270

Bravo

AF:

0.394

Asia WGS

AF:

0.383

AC:

1329

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

403+14T>C in Intron 05 of SLC26A5: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus se quence and has been identified in 29.3% (1096/3738) of African American chromoso mes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs .washington.edu/EVS; dbSNP rs7779997). -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 24, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive nonsyndromic hearing loss 61

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.8

DANN

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over