chr6-35992613-C-T

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.689G>A(p.Ser230Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,613,622 control chromosomes in the GnomAD database, including 12,785 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 0.10 ( 940 hom., cov: 32)

Exomes 𝑓: 0.12 ( 11845 hom. )

Consequence

SLC26A8
NM_052961.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.156

Publications

23 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:

LOC105375035 (HGNC:):

LOC105375035 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=0.0041314363).

BP6

Variant 6-35992613-C-T is Benign according to our data. Variant chr6-35992613-C-T is described in ClinVar as Benign. ClinVar VariationId is 1243863.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A8	NM_052961.4 link	c.689G>A	p.Ser230Asn	missense_variant	Exon 6 of 20	ENST00000490799.6	NP_443193.1	Q96RN1-1A0A024RCV0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC26A8	ENST00000490799.6 link	c.689G>A	p.Ser230Asn	missense_variant	Exon 6 of 20	1	NM_052961.4	ENSP00000417638.1	Q96RN1-1
SLC26A8	ENST00000394602.6 link	c.627+5125G>A		intron_variant	Intron 5 of 17	1		ENSP00000378100.2	Q96RN1-2
SLC26A8	ENST00000355574.6 link	c.689G>A	p.Ser230Asn	missense_variant	Exon 6 of 20	2		ENSP00000347778.2	Q96RN1-1
SLC26A8	ENST00000486155.1 link	n.1044G>A		non_coding_transcript_exon_variant	Exon 6 of 13	2

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

15932

AN:

152110

Hom.:

939

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0438

Gnomad AMI

AF:

0.118

Gnomad AMR

AF:

0.113

Gnomad ASJ

AF:

0.238

Gnomad EAS

AF:

0.0549

Gnomad SAS

AF:

0.107

Gnomad FIN

AF:

0.129

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.132

Gnomad OTH

AF:

0.128

GnomAD2 exomes

AF:

0.120

AC:

29994

AN:

250822

AF XY:

0.122

show subpopulations

Gnomad AFR exome

AF:

0.0390

Gnomad AMR exome

AF:

0.115

Gnomad ASJ exome

AF:

0.227

Gnomad EAS exome

AF:

0.0552

Gnomad FIN exome

AF:

0.131

Gnomad NFE exome

AF:

0.132

Gnomad OTH exome

AF:

0.131

GnomAD4 exome

AF:

0.123

AC:

179702

AN:

1461394

Hom.:

11845

Cov.:

AF XY:

0.123

AC XY:

89614

AN XY:

726998

show subpopulations

African (AFR)

AF:

0.0385

AC:

1289

AN:

33480

American (AMR)

AF:

0.119

AC:

5332

AN:

44660

Ashkenazi Jewish (ASJ)

AF:

0.232

AC:

6047

AN:

26102

East Asian (EAS)

AF:

0.0484

AC:

1920

AN:

39682

South Asian (SAS)

AF:

0.113

AC:

9695

AN:

86176

European-Finnish (FIN)

AF:

0.132

AC:

7060

AN:

53400

Middle Eastern (MID)

AF:

0.167

AC:

963

AN:

5764

European-Non Finnish (NFE)

AF:

0.126

AC:

139885

AN:

1111758

Other (OTH)

AF:

0.124

AC:

7511

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

7951

15902

23854

31805

39756

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4922

9844

14766

19688

24610

<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:

0.105

AC:

15935

AN:

152228

Hom.:

940

Cov.:

AF XY:

0.105

AC XY:

7809

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.0437

AC:

1817

AN:

41558

American (AMR)

AF:

0.113

AC:

1723

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.238

AC:

828

AN:

3472

East Asian (EAS)

AF:

0.0550

AC:

285

AN:

5182

South Asian (SAS)

AF:

0.108

AC:

520

AN:

4824

European-Finnish (FIN)

AF:

0.129

AC:

1366

AN:

10590

Middle Eastern (MID)

AF:

0.150

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.132

AC:

8977

AN:

68006

Other (OTH)

AF:

0.127

AC:

267

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

730

1460

2191

2921

3651

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

360

540

720

900

<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:

0.126

Hom.:

4289

Bravo

AF:

0.102

TwinsUK

AF:

0.130

AC:

481

ALSPAC

AF:

0.121

AC:

467

ESP6500AA

AF:

0.0427

AC:

188

ESP6500EA

AF:

0.133

AC:

1143

ExAC

AF:

0.118

AC:

14348

Asia WGS

AF:

0.0770

AC:

267

AN:

3478

EpiCase

AF:

0.141

EpiControl

AF:

0.133

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

0.086

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.42

CADD

Benign

4.7

(source)

DANN

Benign

0.16

DEOGEN2

Benign

0.37

T;T

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.062

LIST_S2

Benign

0.62

.;T

MetaRNN

Benign

0.0041

T;T

MetaSVM

Benign

-0.71

MutationAssessor

Benign

0.89

L;L

PhyloP100

-0.16

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.32

N;N

REVEL

Benign

0.18

Sift

Benign

0.27

T;T

Sift4G

Benign

0.28

T;T

Polyphen

0.031

B;B

Vest4

0.032

MPC

0.21

ClinPred

0.0043

GERP RS

3.3

Varity_R

0.073

gMVP

0.56

Mutation Taster

=92/8

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over