rs117444825

Positions:

chr7-103393049-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_198999.3(SLC26A5):c.989A>G(p.Asn330Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0162 in 1,613,928 control chromosomes in the GnomAD database, including 262 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N330D) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0095 ( 9 hom., cov: 32)

Exomes 𝑓: 0.017 ( 253 hom. )

Consequence

SLC26A5
NM_198999.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 2.24

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:

SLC26A5 (HGNC:):

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 (MetaRNN=0.0103934705).

BP6

Variant 7-103393049-T-C is Benign according to our data. Variant chr7-103393049-T-C is described in ClinVar as [Benign]. Clinvar id is 48341.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00948 (1444/152280) while in subpopulation NFE AF= 0.0169 (1148/68018). AF 95% confidence interval is 0.0161. There are 9 homozygotes in gnomad4. There are 653 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC26A5	NM_198999.3 linkuse as main transcript	c.989A>G	p.Asn330Ser	missense_variant	10/20	ENST00000306312.8	NP_945350.1	P58743-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC26A5	ENST00000306312.8 linkuse as main transcript	c.989A>G	p.Asn330Ser	missense_variant	10/20	1	NM_198999.3	ENSP00000304783.3	P58743-1
SLC26A5	ENST00000393727.5 linkuse as main transcript	c.989A>G	p.Asn330Ser	missense_variant	8/18	1		ENSP00000377328.1	Q7Z7F4
SLC26A5	ENST00000393723.2 linkuse as main transcript	c.989A>G	p.Asn330Ser	missense_variant	8/17	1		ENSP00000377324.1	P58743-6

Frequencies

GnomAD3 genomes

AF:

0.00949

AC:

1444

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00287

Gnomad AMI

AF:

0.0241

Gnomad AMR

AF:

0.00268

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00895

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0169

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00978

AC:

2457

AN:

251122

Hom.:

AF XY:

0.00960

AC XY:

1303

AN XY:

135732

show subpopulations

Gnomad AFR exome

AF:

0.00265

Gnomad AMR exome

AF:

0.00214

Gnomad ASJ exome

AF:

0.000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00961

Gnomad NFE exome

AF:

0.0182

Gnomad OTH exome

AF:

0.00848

GnomAD4 exome

AF:

0.0169

AC:

24638

AN:

1461648

Hom.:

253

Cov.:

AF XY:

0.0161

AC XY:

11677

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.00284

Gnomad4 AMR exome

AF:

0.00215

Gnomad4 ASJ exome

AF:

0.000995

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.0105

Gnomad4 NFE exome

AF:

0.0207

Gnomad4 OTH exome

AF:

0.0124

GnomAD4 genome

AF:

0.00948

AC:

1444

AN:

152280

Hom.:

Cov.:

AF XY:

0.00877

AC XY:

653

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00286

Gnomad4 AMR

AF:

0.00268

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00895

Gnomad4 NFE

AF:

0.0169

Gnomad4 OTH

AF:

0.00614

Alfa

AF:

0.0143

Hom.:

Bravo

AF:

0.00894

TwinsUK

AF:

0.0194

AC:

ALSPAC

AF:

0.0202

AC:

ESP6500AA

AF:

0.00363

AC:

ESP6500EA

AF:

0.0169

AC:

145

ExAC

AF:

0.0108

AC:

1313

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0153

EpiControl

AF:

0.0151

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 20, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Mar 13, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 07, 2012	Asn330Ser in Exon 10 of SLC26A5: This variant is not expected to have clinical s ignificance because it has been identified in 1.7% (121/7020) of European Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS; dbSNP rs117444825). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Autosomal recessive nonsyndromic hearing loss 61

Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Aug 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.39

.;.;.;T;.;T;.;T;.

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.56

LIST_S2

Uncertain

0.96

D;D;.;D;D;D;D;.;D

MetaRNN

Benign

0.010

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.45

MutationAssessor

Benign

-0.26

N;N;N;N;N;.;.;.;N

PrimateAI

Uncertain

0.53

PROVEAN

Benign

0.83

N;N;N;N;N;.;N;N;N

REVEL

Benign

0.19

Sift

Benign

0.068

T;T;T;T;T;.;T;T;T

Sift4G

Benign

0.13

T;T;T;T;T;T;T;T;T

Polyphen

0.10

B;B;.;B;.;.;.;.;.

Vest4

0.14

MPC

0.19

ClinPred

0.013

GERP RS

3.2

Varity_R

0.049

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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