rs142639517

Positions:

chr7-103389401-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_198999.3(SLC26A5):c.1335T>C(p.Ile445Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00526 in 1,614,050 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0035 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0055 ( 33 hom. )

Consequence

SLC26A5
NM_198999.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.864

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 7-103389401-A-G is Benign according to our data. Variant chr7-103389401-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 165270.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-103389401-A-G is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.864 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00345 (526/152312) while in subpopulation NFE AF= 0.00601 (409/68028). AF 95% confidence interval is 0.00553. There are 3 homozygotes in gnomad4. There are 221 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC26A5	NM_198999.3 linkuse as main transcript	c.1335T>C	p.Ile445Ile	synonymous_variant	13/20	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.1335T>C	p.Ile445Ile	synonymous_variant	13/20	1	NM_198999.3	ENSP00000304783.3	P58743-1
SLC26A5	ENST00000393727.5 linkuse as main transcript	c.1335T>C	p.Ile445Ile	synonymous_variant	11/18	1		ENSP00000377328.1	Q7Z7F4
SLC26A5	ENST00000393723.2 linkuse as main transcript	c.1312-287T>C		intron_variant		1		ENSP00000377324.1	P58743-6

Frequencies

GnomAD3 genomes

AF:

0.00346

AC:

526

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00123

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00264

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00601

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00350

AC:

879

AN:

251488

Hom.:

AF XY:

0.00352

AC XY:

478

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.00387

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00351

Gnomad NFE exome

AF:

0.00595

Gnomad OTH exome

AF:

0.00456

GnomAD4 exome

AF:

0.00545

AC:

7971

AN:

1461738

Hom.:

Cov.:

AF XY:

0.00526

AC XY:

3826

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.00122

Gnomad4 AMR exome

AF:

0.00101

Gnomad4 ASJ exome

AF:

0.00398

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000243

Gnomad4 FIN exome

AF:

0.00316

Gnomad4 NFE exome

AF:

0.00655

Gnomad4 OTH exome

AF:

0.00497

GnomAD4 genome

AF:

0.00345

AC:

526

AN:

152312

Hom.:

Cov.:

AF XY:

0.00297

AC XY:

221

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00123

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00264

Gnomad4 NFE

AF:

0.00601

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00501

Hom.:

Bravo

AF:

0.00325

EpiCase

AF:

0.00578

EpiControl

AF:

0.00575

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 09, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2023	SLC26A5: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 10, 2018	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Apr 30, 2012	Ile445Ile in Exon 13 of SLC26A5: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located with in the splice consensus sequence, and has been identified in 0.6% (43/7020) of E uropean American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS; dbSNP rs142639517). -
Likely benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 08, 2016	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

2.9

DANN

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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