Variant 8-91249722-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_052832.4(SLC26A7):c.71T>C(p.Ile24Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000856 in 1,608,860 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00088 ( 1 hom. )

Consequence

SLC26A7
NM_052832.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.23

Variant links:

Genes affected

SLC26A7 (HGNC:14467): (solute carrier family 26 member 7) This gene is one member of a family of sulfate/anion transporter genes. Family members are well conserved in gene structure and protein length yet have markedly different tissue expression patterns. This gene has abundant and specific expression in the kidney. Alternatively spliced transcript variants that encode different isoforms have been described. [provided by RefSeq, Aug 2013]

SLC26A7 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.013024986).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC26A7	NM_052832.4 linkuse as main transcript	c.71T>C	p.Ile24Thr	missense_variant	2/19	ENST00000276609.8	NP_439897.1	Q8TE54-1
SLC26A7	NM_134266.2 linkuse as main transcript	c.71T>C	p.Ile24Thr	missense_variant	2/19		NP_599028.1	Q8TE54-2
SLC26A7	NM_001282356.2 linkuse as main transcript	c.71T>C	p.Ile24Thr	missense_variant	3/20		NP_001269285.1	Q8TE54-1
SLC26A7	NM_001282357.2 linkuse as main transcript	c.-750T>C		5_prime_UTR_variant	3/19		NP_001269286.1	Q8TE54A0A087WZI7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC26A7	ENST00000276609.8 linkuse as main transcript	c.71T>C	p.Ile24Thr	missense_variant	2/19	1	NM_052832.4	ENSP00000276609.3		Q8TE54-1

Frequencies

GnomAD3 genomes

AF:

0.000585

AC:

AN:

152044

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.000918

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000883

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000822

AC:

203

AN:

246850

Hom.:

AF XY:

0.000801

AC XY:

107

AN XY:

133526

show subpopulations

Gnomad AFR exome

AF:

0.000126

Gnomad AMR exome

AF:

0.000541

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000333

Gnomad FIN exome

AF:

0.000510

Gnomad NFE exome

AF:

0.00138

Gnomad OTH exome

AF:

0.00117

GnomAD4 exome

AF:

0.000884

AC:

1288

AN:

1456816

Hom.:

Cov.:

AF XY:

0.000864

AC XY:

626

AN XY:

724682

show subpopulations

Gnomad4 AFR exome

AF:

0.000212

Gnomad4 AMR exome

AF:

0.000704

Gnomad4 ASJ exome

AF:

0.0000385

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000246

Gnomad4 FIN exome

AF:

0.000543

Gnomad4 NFE exome

AF:

0.00105

Gnomad4 OTH exome

AF:

0.000565

GnomAD4 genome

AF:

0.000585

AC:

AN:

152044

Hom.:

Cov.:

AF XY:

0.000525

AC XY:

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.000918

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.000883

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000822

Hom.:

Bravo

AF:

0.000835

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.00106

AC:

129

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 05, 2024

The c.71T>C (p.I24T) alteration is located in exon 2 (coding exon 1) of the SLC26A7 gene. This alteration results from a T to C substitution at nucleotide position 71, causing the isoleucine (I) at amino acid position 24 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.12

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.035

.;T;T;T;.

Eigen

Benign

-0.13

Eigen_PC

Benign

0.070

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.76

T;.;T;.;T

M_CAP

Benign

0.054

MetaRNN

Benign

0.013

T;T;T;T;T

MetaSVM

Uncertain

0.021

MutationAssessor

Benign

0.81

.;L;L;L;L

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.020

N;N;.;N;N

REVEL

Uncertain

0.33

Sift

Benign

0.13

T;T;.;T;T

Sift4G

Uncertain

0.017

D;D;D;D;D

Polyphen

0.079, 0.13

.;B;B;B;B

Vest4

0.45, 0.45

MVP

0.83

MPC

0.19

ClinPred

0.019

GERP RS

5.5

Varity_R

0.11

gMVP

0.30

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