Genetic Variant SLC26A8:p.Val73Met (chr6-36012344-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_052961.4(SLC26A8):c.217G>A(p.Val73Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 1,600,438 control chromosomes in the GnomAD database, including 48,900 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.29 ( 6875 hom., cov: 32)

Exomes 𝑓: 0.24 ( 42025 hom. )

Consequence

SLC26A8
NM_052961.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0250

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:

LOC105375034 (HGNC:):

LOC105375034 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0010611117).

BP6

Variant 6-36012344-C-T is Benign according to our data. Variant chr6-36012344-C-T is described in ClinVar as [Benign]. Clinvar id is 1245672.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A8	NM_052961.4 link	c.217G>A	p.Val73Met	missense_variant	Exon 3 of 20	ENST00000490799.6	NP_443193.1	Q96RN1-1A0A024RCV0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC26A8	ENST00000490799.6 link	c.217G>A	p.Val73Met	missense_variant	Exon 3 of 20	1	NM_052961.4	ENSP00000417638.1		Q96RN1-1

Frequencies

GnomAD3 genomes

AF:

0.289

AC:

43855

AN:

151846

Hom.:

6856

Cov.:

show subpopulations

Gnomad AFR

AF:

0.426

Gnomad AMI

AF:

0.191

Gnomad AMR

AF:

0.233

Gnomad ASJ

AF:

0.322

Gnomad EAS

AF:

0.105

Gnomad SAS

AF:

0.182

Gnomad FIN

AF:

0.238

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.246

Gnomad OTH

AF:

0.319

GnomAD3 exomes

AF:

0.234

AC:

55656

AN:

237844

Hom.:

7199

AF XY:

0.229

AC XY:

29566

AN XY:

129136

show subpopulations

Gnomad AFR exome

AF:

0.420

Gnomad AMR exome

AF:

0.188

Gnomad ASJ exome

AF:

0.319

Gnomad EAS exome

AF:

0.108

Gnomad SAS exome

AF:

0.181

Gnomad FIN exome

AF:

0.244

Gnomad NFE exome

AF:

0.243

Gnomad OTH exome

AF:

0.252

GnomAD4 exome

AF:

0.236

AC:

341220

AN:

1448474

Hom.:

42025

Cov.:

AF XY:

0.233

AC XY:

168235

AN XY:

720588

show subpopulations

Gnomad4 AFR exome

AF:

0.425

Gnomad4 AMR exome

AF:

0.196

Gnomad4 ASJ exome

AF:

0.322

Gnomad4 EAS exome

AF:

0.107

Gnomad4 SAS exome

AF:

0.183

Gnomad4 FIN exome

AF:

0.254

Gnomad4 NFE exome

AF:

0.237

Gnomad4 OTH exome

AF:

0.241

GnomAD4 genome

AF:

0.289

AC:

43917

AN:

151964

Hom.:

6875

Cov.:

AF XY:

0.286

AC XY:

21204

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.426

Gnomad4 AMR

AF:

0.233

Gnomad4 ASJ

AF:

0.322

Gnomad4 EAS

AF:

0.104

Gnomad4 SAS

AF:

0.183

Gnomad4 FIN

AF:

0.238

Gnomad4 NFE

AF:

0.246

Gnomad4 OTH

AF:

0.321

Alfa

AF:

0.249

Hom.:

11954

Bravo

AF:

0.296

TwinsUK

AF:

0.241

AC:

892

ALSPAC

AF:

0.243

AC:

936

ESP6500AA

AF:

0.412

AC:

1815

ESP6500EA

AF:

0.246

AC:

2119

ExAC

AF:

0.238

AC:

28944

Asia WGS

AF:

0.207

AC:

721

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.73

CADD

Benign

8.8

DANN

Benign

0.37

DEOGEN2

Benign

0.046

T;.;T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0050

LIST_S2

Benign

0.20

.;T;T;T

MetaRNN

Benign

0.0011

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.8

N;N;N;.

PrimateAI

Benign

0.37

PROVEAN

Benign

0.66

N;N;N;N

REVEL

Benign

0.020

Sift

Benign

0.95

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0030

B;B;B;.

Vest4

0.056

MPC

0.21

ClinPred

0.00046

GERP RS

-2.6

Varity_R

0.024

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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