Variant 8-91289142-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_052832.4(SLC26A7):c.200C>T(p.Ala67Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,460,330 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

SLC26A7
NM_052832.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.18

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_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.955

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SLC26A7	NM_052832.4 linkuse as main transcript	c.200C>T	p.Ala67Val	missense_variant	3/19	ENST00000276609.8	NP_439897.1
SLC26A7	NM_134266.2 linkuse as main transcript	c.200C>T	p.Ala67Val	missense_variant	3/19		NP_599028.1
SLC26A7	NM_001282356.2 linkuse as main transcript	c.200C>T	p.Ala67Val	missense_variant	4/20		NP_001269285.1
SLC26A7	NM_001282357.2 linkuse as main transcript	c.-621C>T		5_prime_UTR_variant	4/19		NP_001269286.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC26A7	ENST00000276609.8 linkuse as main transcript	c.200C>T	p.Ala67Val	missense_variant	3/19	1	NM_052832.4	ENSP00000276609	P1	Q8TE54-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1460330

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726564

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000564

Hom.:

Bravo

AF:

0.00000378

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 21, 2023

The c.200C>T (p.A67V) alteration is located in exon 3 (coding exon 2) of the SLC26A7 gene. This alteration results from a C to T substitution at nucleotide position 200, causing the alanine (A) at amino acid position 67 to be replaced by a valine (V). 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

Pathogenic

0.81

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.17

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.92

.;D;D;D;.

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.78

LIST_S2

Uncertain

0.89

D;.;D;.;D

M_CAP

Uncertain

0.29

MetaRNN

Pathogenic

0.96

D;D;D;D;D

MetaSVM

Uncertain

0.75

MutationAssessor

Uncertain

2.8

.;M;M;M;M

MutationTaster

Benign

0.88

N;N;N

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-3.8

D;D;.;D;D

REVEL

Pathogenic

0.65

Sift

Uncertain

0.0010

D;D;.;D;D

Sift4G

Uncertain

0.0090

D;D;D;D;D

Polyphen

0.82, 0.68

.;P;P;P;P

Vest4

0.83

MutPred

0.90

Loss of helix (P = 0.3949);Loss of helix (P = 0.3949);Loss of helix (P = 0.3949);Loss of helix (P = 0.3949);Loss of helix (P = 0.3949);

MVP

0.87

MPC

0.37

ClinPred

0.99

GERP RS

5.3

Varity_R

0.69

gMVP

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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