rs2295852

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_052961.4(SLC26A8):c.1915A>G(p.Ile639Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 1,613,794 control chromosomes in the GnomAD database, including 107,216 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.42 ( 15087 hom., cov: 31)

Exomes 𝑓: 0.35 ( 92129 hom. )

Consequence

SLC26A8
NM_052961.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.34

Publications

29 publications found

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 Gene-Disease associations (from GenCC):

non-syndromic male infertility due to sperm motility disorder
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
spermatogenic failure 3
Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

SLC26A8 links:

ENSG00000304790 (HGNC:):

ENSG00000304790 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.815994E-6).

BP6

Variant 6-35955469-T-C is Benign according to our data. Variant chr6-35955469-T-C is described in ClinVar as Benign. ClinVar VariationId is 1234924.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052961.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC26A8	NM_052961.4	MANE Select	c.1915A>G	p.Ile639Val	missense	Exon 17 of 20	NP_443193.1
SLC26A8	NM_001193476.2		c.1915A>G	p.Ile639Val	missense	Exon 17 of 20	NP_001180405.1
SLC26A8	NM_138718.3		c.1600A>G	p.Ile534Val	missense	Exon 15 of 18	NP_619732.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC26A8	ENST00000490799.6	TSL:1 MANE Select	c.1915A>G	p.Ile639Val	missense	Exon 17 of 20	ENSP00000417638.1
SLC26A8	ENST00000394602.6	TSL:1	c.1600A>G	p.Ile534Val	missense	Exon 15 of 18	ENSP00000378100.2
SLC26A8	ENST00000355574.6	TSL:2	c.1915A>G	p.Ile639Val	missense	Exon 17 of 20	ENSP00000347778.2

Frequencies

GnomAD3 genomes

AF:

0.420

AC:

63777

AN:

151864

Hom.:

15044

Cov.:

show subpopulations

Gnomad AFR

AF:

0.646

Gnomad AMI

AF:

0.407

Gnomad AMR

AF:

0.323

Gnomad ASJ

AF:

0.318

Gnomad EAS

AF:

0.295

Gnomad SAS

AF:

0.292

Gnomad FIN

AF:

0.308

Gnomad MID

AF:

0.462

Gnomad NFE

AF:

0.345

Gnomad OTH

AF:

0.428

GnomAD2 exomes

AF:

0.335

AC:

84110

AN:

251336

AF XY:

0.333

show subpopulations

Gnomad AFR exome

AF:

0.650

Gnomad AMR exome

AF:

0.215

Gnomad ASJ exome

AF:

0.324

Gnomad EAS exome

AF:

0.296

Gnomad FIN exome

AF:

0.315

Gnomad NFE exome

AF:

0.350

Gnomad OTH exome

AF:

0.345

GnomAD4 exome

AF:

0.349

AC:

510559

AN:

1461812

Hom.:

92129

Cov.:

AF XY:

0.346

AC XY:

251855

AN XY:

727204

show subpopulations

African (AFR)

AF:

0.656

AC:

21954

AN:

33480

American (AMR)

AF:

0.230

AC:

10289

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.325

AC:

8490

AN:

26130

East Asian (EAS)

AF:

0.280

AC:

11135

AN:

39700

South Asian (SAS)

AF:

0.283

AC:

24436

AN:

86258

European-Finnish (FIN)

AF:

0.318

AC:

16981

AN:

53418

Middle Eastern (MID)

AF:

0.425

AC:

2452

AN:

5768

European-Non Finnish (NFE)

AF:

0.354

AC:

393303

AN:

1111946

Other (OTH)

AF:

0.356

AC:

21519

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

19150

38301

57451

76602

95752

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12626

25252

37878

50504

63130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.420

AC:

63863

AN:

151982

Hom.:

15087

Cov.:

AF XY:

0.414

AC XY:

30730

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.647

AC:

26784

AN:

41426

American (AMR)

AF:

0.323

AC:

4923

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.318

AC:

1105

AN:

3470

East Asian (EAS)

AF:

0.295

AC:

1520

AN:

5158

South Asian (SAS)

AF:

0.291

AC:

1404

AN:

4822

European-Finnish (FIN)

AF:

0.308

AC:

3255

AN:

10562

Middle Eastern (MID)

AF:

0.456

AC:

134

AN:

294

European-Non Finnish (NFE)

AF:

0.345

AC:

23462

AN:

67966

Other (OTH)

AF:

0.429

AC:

905

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1745

3489

5234

6978

8723

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

568

1136

1704

2272

2840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.371

Hom.:

39026

Bravo

AF:

0.435

TwinsUK

AF:

0.357

AC:

1324

ALSPAC

AF:

0.361

AC:

1390

ESP6500AA

AF:

0.637

AC:

2807

ESP6500EA

AF:

0.349

AC:

3003

ExAC

AF:

0.346

AC:

41971

Asia WGS

AF:

0.309

AC:

1074

AN:

3478

EpiCase

AF:

0.359

EpiControl

AF:

0.358

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.37

CADD

Benign

0.0010

(source)

DANN

Benign

0.28

DEOGEN2

Benign

0.096

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.25

MetaRNN

Benign

0.0000028

MetaSVM

Benign

-0.57

MutationAssessor

Benign

0.46

PhyloP100

-1.3

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.020

REVEL

Benign

0.21

Sift

Benign

0.98

Sift4G

Benign

0.41

Polyphen

0.0

Vest4

0.028

MPC

0.18

ClinPred

0.00059

GERP RS

-5.0

Varity_R

0.023

gMVP

0.37

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over