rs36039758

Positions:

chr7-107683506-A-T

Variant summary

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

The NM_000441.2(SLC26A4):c.970A>T(p.Asn324Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0018 in 1,613,876 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0097 ( 24 hom., cov: 32)

Exomes 𝑓: 0.00098 ( 24 hom. )

Consequence

SLC26A4
NM_000441.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12O:1

Conservation

PhyloP100: 4.50

Variant links:

Genes affected

SLC26A4 (HGNC:8818): (solute carrier family 26 member 4) Mutations in this gene are associated with Pendred syndrome, the most common form of syndromic deafness, an autosomal-recessive disease. It is highly homologous to the SLC26A3 gene; they have similar genomic structures and this gene is located 3' of the SLC26A3 gene. The encoded protein has homology to sulfate transporters. [provided by RefSeq, Jul 2008]

SLC26A4 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=0.0110755265).

BP6

Variant 7-107683506-A-T is Benign according to our data. Variant chr7-107683506-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 43574.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-107683506-A-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00972 (1480/152298) while in subpopulation AFR AF= 0.0341 (1418/41558). AF 95% confidence interval is 0.0326. There are 24 homozygotes in gnomad4. There are 719 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 24 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC26A4	NM_000441.2 linkuse as main transcript	c.970A>T	p.Asn324Tyr	missense_variant	8/21	ENST00000644269.2	NP_000432.1	O43511-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC26A4	ENST00000644269.2 linkuse as main transcript	c.970A>T	p.Asn324Tyr	missense_variant	8/21		NM_000441.2	ENSP00000494017.1		O43511-1

Frequencies

GnomAD3 genomes

AF:

0.00970

AC:

1476

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0341

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00243

AC:

610

AN:

250854

Hom.:

AF XY:

0.00198

AC XY:

268

AN XY:

135554

show subpopulations

Gnomad AFR exome

AF:

0.0342

Gnomad AMR exome

AF:

0.000926

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000132

Gnomad OTH exome

AF:

0.000655

GnomAD4 exome

AF:

0.000978

AC:

1430

AN:

1461578

Hom.:

Cov.:

AF XY:

0.000828

AC XY:

602

AN XY:

727082

show subpopulations

Gnomad4 AFR exome

AF:

0.0353

Gnomad4 AMR exome

AF:

0.00103

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000791

Gnomad4 OTH exome

AF:

0.00162

GnomAD4 genome

AF:

0.00972

AC:

1480

AN:

152298

Hom.:

Cov.:

AF XY:

0.00965

AC XY:

719

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0341

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00144

Hom.:

Bravo

AF:

0.0111

ESP6500AA

AF:

0.0268

AC:

118

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00310

AC:

376

Asia WGS

AF:

0.00173

AC:

AN:

3476

EpiCase

AF:

0.000273

EpiControl

AF:

0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:12Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This variant is associated with the following publications: (PMID: 31599023, 27771369, 30245029, 26485571, 14679580, 24224479, 20981092, 25262649) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 05, 2019	The p.Asn324Tyr variant in SLC26A4 is classified as benign because it has been identified in 3.4% (847/24956) of African chromosomes by gnomAD (http://gnomad.broadinstitute.org/). ACMG/AMP criteria applied: BA1. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 03, 2016	- -

Pendred syndrome

Benign:3

Likely benign, criteria provided, single submitter	literature only	Counsyl	Apr 26, 2014	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Jan 10, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -

Autosomal recessive nonsyndromic hearing loss 4

Benign:1Other:1

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -
other, no assertion criteria provided	in vitro;literature only	National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center	Aug 20, 2019	Benign effect in vitro experiment Benign effect in vitro experiment

Pendred syndrome;C3538946:Autosomal recessive nonsyndromic hearing loss 4

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Feb 18, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.75

D;D

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.84

.;T

MetaRNN

Benign

0.011

T;T

MetaSVM

Uncertain

0.30

MutationAssessor

Uncertain

2.8

M;M

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-5.0

D;.

REVEL

Pathogenic

0.78

Sift

Uncertain

0.0050

D;.

Sift4G

Uncertain

0.031

D;.

Polyphen

1.0

D;D

Vest4

0.82

MVP

0.99

MPC

0.075

ClinPred

0.043

GERP RS

4.5

Varity_R

0.71

gMVP

0.87

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