rs61741366

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_052961.4(SLC26A8):c.2734C>T(p.Pro912Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0108 in 1,614,056 control chromosomes in the GnomAD database, including 121 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0080 ( 7 hom., cov: 32)

Exomes 𝑓: 0.011 ( 114 hom. )

Consequence

SLC26A8
NM_052961.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.48

Publications

8 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: STRONG, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia
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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003974676).

BP6

Variant 6-35944079-G-A is Benign according to our data. Variant chr6-35944079-G-A is described in ClinVar as Benign. ClinVar VariationId is 2656511.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 7 AD,AR gene

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	UniProt
SLC26A8	NM_052961.4	MANE Select	c.2734C>T	p.Pro912Ser	missense	Exon 20 of 20	NP_443193.1	Q96RN1-1
SLC26A8	NM_001193476.2		c.2734C>T	p.Pro912Ser	missense	Exon 20 of 20	NP_001180405.1	Q96RN1-1
SLC26A8	NM_138718.3		c.2419C>T	p.Pro807Ser	missense	Exon 18 of 18	NP_619732.2	Q96RN1-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC26A8	ENST00000490799.6	TSL:1 MANE Select	c.2734C>T	p.Pro912Ser	missense	Exon 20 of 20	ENSP00000417638.1	Q96RN1-1
SLC26A8	ENST00000394602.6	TSL:1	c.2419C>T	p.Pro807Ser	missense	Exon 18 of 18	ENSP00000378100.2	Q96RN1-2
SLC26A8	ENST00000355574.6	TSL:2	c.2734C>T	p.Pro912Ser	missense	Exon 20 of 20	ENSP00000347778.2	Q96RN1-1

Frequencies

GnomAD3 genomes

AF:

0.00804

AC:

1222

AN:

152046

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00208

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.00603

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00872

Gnomad FIN

AF:

0.0172

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0112

Gnomad OTH

AF:

0.0115

GnomAD2 exomes

AF:

0.00966

AC:

2429

AN:

251486

AF XY:

0.00995

show subpopulations

Gnomad AFR exome

AF:

0.00209

Gnomad AMR exome

AF:

0.00491

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.0167

Gnomad NFE exome

AF:

0.0130

Gnomad OTH exome

AF:

0.0114

GnomAD4 exome

AF:

0.0111

AC:

16189

AN:

1461892

Hom.:

114

Cov.:

AF XY:

0.0109

AC XY:

7946

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.00164

AC:

AN:

33480

American (AMR)

AF:

0.00541

AC:

242

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00145

AC:

AN:

26136

East Asian (EAS)

AF:

0.000151

AC:

AN:

39700

South Asian (SAS)

AF:

0.00996

AC:

859

AN:

86258

European-Finnish (FIN)

AF:

0.0178

AC:

951

AN:

53420

Middle Eastern (MID)

AF:

0.0106

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0119

AC:

13260

AN:

1112010

Other (OTH)

AF:

0.0119

AC:

717

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

1057

2114

3170

4227

5284

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

494

988

1482

1976

2470

<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:

0.00802

AC:

1221

AN:

152164

Hom.:

Cov.:

AF XY:

0.00776

AC XY:

577

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.00207

AC:

AN:

41516

American (AMR)

AF:

0.00602

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5174

South Asian (SAS)

AF:

0.00852

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.0172

AC:

182

AN:

10602

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0112

AC:

760

AN:

67992

Other (OTH)

AF:

0.0114

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

132

198

264

330

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00998

Hom.:

Bravo

AF:

0.00728

TwinsUK

AF:

0.0119

AC:

ALSPAC

AF:

0.0109

AC:

ESP6500AA

AF:

0.00295

AC:

ESP6500EA

AF:

0.0117

AC:

101

ExAC

AF:

0.0103

AC:

1252

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

ClinVar submissions

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

0.092

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.56

CADD

Benign

7.4

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.060

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.47

MetaRNN

Benign

0.0040

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

PhyloP100

1.5

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.9

REVEL

Benign

0.047

Sift

Benign

0.30

Sift4G

Uncertain

0.023

Polyphen

0.079

Vest4

0.23

MPC

0.70

ClinPred

0.0080

GERP RS

0.51

Varity_R

0.058

gMVP

0.27

Mutation Taster

=99/1

polymorphism

(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

Computational scores

Splicing

Publications

Other links and lift over