Variant chr8-91295625-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000276609.8(SLC26A7):c.399C>A(p.Ser133Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,614,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

SLC26A7
ENST00000276609.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.237

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25213304).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SLC26A7	NM_052832.4 linkuse as main transcript	c.399C>A	p.Ser133Arg	missense_variant	4/19	ENST00000276609.8	NP_439897.1
SLC26A7	NM_134266.2 linkuse as main transcript	c.399C>A	p.Ser133Arg	missense_variant	4/19		NP_599028.1
SLC26A7	NM_001282356.2 linkuse as main transcript	c.399C>A	p.Ser133Arg	missense_variant	5/20		NP_001269285.1
SLC26A7	NM_001282357.2 linkuse as main transcript	c.-422C>A		5_prime_UTR_variant	5/19		NP_001269286.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC26A7	ENST00000276609.8 linkuse as main transcript	c.399C>A	p.Ser133Arg	missense_variant	4/19	1	NM_052832.4	ENSP00000276609	P1	Q8TE54-1

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000597

AC:

AN:

251434

Hom.:

AF XY:

0.0000515

AC XY:

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.000231

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1461800

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152300

Hom.:

Cov.:

AF XY:

0.0000671

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000982

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Nov 10, 2022

The c.399C>A (p.S133R) alteration is located in exon 4 (coding exon 3) of the SLC26A7 gene. This alteration results from a C to A substitution at nucleotide position 399, causing the serine (S) at amino acid position 133 to be replaced by an arginine (R). 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

0.17

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.73

.;D;D;D;.

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.71

T;.;T;.;T

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.25

T;T;T;T;T

MetaSVM

Uncertain

-0.015

MutationAssessor

Benign

1.9

.;M;M;M;M

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-2.3

N;D;.;D;D

REVEL

Uncertain

0.43

Sift

Benign

0.054

T;D;.;D;D

Sift4G

Uncertain

0.038

D;D;D;D;D

Polyphen

0.70, 0.88

.;P;P;P;P

Vest4

0.36, 0.36, 0.36, 0.35

MutPred

0.22

Loss of disorder (P = 0.0765);Loss of disorder (P = 0.0765);Loss of disorder (P = 0.0765);Loss of disorder (P = 0.0765);Loss of disorder (P = 0.0765);

MVP

0.54

MPC

0.37

ClinPred

0.13

GERP RS

-2.3

Varity_R

0.43

gMVP

0.53

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