Variant 6-36012301-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP5BP4BS2_Supporting

The NM_052961.4(SLC26A8):c.260G>A(p.Arg87Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00069 in 1,612,042 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00073 ( 1 hom. )

Consequence

SLC26A8
NM_052961.4 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 1.15

Variant links:

Genes affected

SLC26A8 (HGNC:14468): (solute carrier family 26 member 8) This gene encodes a member of the SLC26 gene family of anion transporters. Family members are well conserved in gene structure and protein length yet have markedly different tissue expression patterns. The expression of this gene appears to be restricted to spermatocytes. Alternatively spliced transcript variants that encode different isoforms have been described. [provided by RefSeq, Jul 2010]

SLC26A8 links:

SLC26A8 (HGNC:):

SLC26A8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PP5

Variant 6-36012301-C-T is Pathogenic according to our data. Variant chr6-36012301-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 50909.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-36012301-C-T is described in Lovd as [Likely_pathogenic].

BP4

Computational evidence support a benign effect (MetaRNN=0.21989736). . Strength limited to SUPPORTING due to the PP5.

BS2

High AC in GnomAd4 at 44 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC26A8	NM_052961.4 linkuse as main transcript	c.260G>A	p.Arg87Gln	missense_variant	3/20	ENST00000490799.6	NP_443193.1	Q96RN1-1A0A024RCV0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC26A8	ENST00000490799.6 linkuse as main transcript	c.260G>A	p.Arg87Gln	missense_variant	3/20	1	NM_052961.4	ENSP00000417638.1		Q96RN1-1

Frequencies

GnomAD3 genomes

AF:

0.000289

AC:

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000309

AC:

AN:

249036

Hom.:

AF XY:

0.000319

AC XY:

AN XY:

134790

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000448

Gnomad ASJ exome

AF:

0.000601

Gnomad EAS exome

AF:

0.0000549

Gnomad SAS exome

AF:

0.000231

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000424

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000732

AC:

1069

AN:

1459780

Hom.:

Cov.:

AF XY:

0.000680

AC XY:

494

AN XY:

726264

show subpopulations

Gnomad4 AFR exome

AF:

0.0000600

Gnomad4 AMR exome

AF:

0.000363

Gnomad4 ASJ exome

AF:

0.000690

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.000175

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000886

Gnomad4 OTH exome

AF:

0.000514

GnomAD4 genome

AF:

0.000289

AC:

AN:

152262

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000485

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000473

Hom.:

Bravo

AF:

0.000344

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000354

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000890

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Spermatogenic failure 3

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

May 02, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.0024

BayesDel_noAF

Uncertain

0.090

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

T;.;T;.

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.81

.;T;T;T

M_CAP

Pathogenic

0.36

MetaRNN

Benign

0.22

T;T;T;T

MetaSVM

Uncertain

-0.18

MutationAssessor

Benign

1.1

L;L;L;.

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.9

N;N;N;D

REVEL

Uncertain

0.53

Sift

Benign

0.17

T;T;T;D

Sift4G

Benign

0.16

T;T;T;T

Polyphen

0.92

P;D;P;.

Vest4

0.21

MVP

0.74

MPC

0.70

ClinPred

0.073

GERP RS

4.8

Varity_R

0.22

gMVP

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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