6-35951188-C-T

Variant names:

Variant summary

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

The NM_052961.4(SLC26A8):c.2447G>A(p.Arg816Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 1,613,726 control chromosomes in the GnomAD database, including 112 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R816W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0068 ( 6 hom., cov: 31)

Exomes 𝑓: 0.011 ( 106 hom. )

Consequence

SLC26A8
NM_052961.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.212

Publications

5 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=0.003674239).

BP6

Variant 6-35951188-C-T is Benign according to our data. Variant chr6-35951188-C-T is described in ClinVar as Benign. ClinVar VariationId is 788857.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 6 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.2447G>A	p.Arg816Gln	missense	Exon 19 of 20	NP_443193.1	Q96RN1-1
SLC26A8	NM_001193476.2		c.2447G>A	p.Arg816Gln	missense	Exon 19 of 20	NP_001180405.1	Q96RN1-1
SLC26A8	NM_138718.3		c.2132G>A	p.Arg711Gln	missense	Exon 17 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.2447G>A	p.Arg816Gln	missense	Exon 19 of 20	ENSP00000417638.1	Q96RN1-1
SLC26A8	ENST00000394602.6	TSL:1	c.2132G>A	p.Arg711Gln	missense	Exon 17 of 18	ENSP00000378100.2	Q96RN1-2
SLC26A8	ENST00000355574.6	TSL:2	c.2447G>A	p.Arg816Gln	missense	Exon 19 of 20	ENSP00000347778.2	Q96RN1-1

Frequencies

GnomAD3 genomes

AF:

0.00681

AC:

1034

AN:

151832

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00230

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00342

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.00869

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0113

Gnomad OTH

AF:

0.00385

GnomAD2 exomes

AF:

0.00679

AC:

1706

AN:

251422

AF XY:

0.00695

show subpopulations

Gnomad AFR exome

AF:

0.00203

Gnomad AMR exome

AF:

0.00295

Gnomad ASJ exome

AF:

0.00595

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00929

Gnomad NFE exome

AF:

0.0109

Gnomad OTH exome

AF:

0.00718

GnomAD4 exome

AF:

0.0105

AC:

15398

AN:

1461776

Hom.:

106

Cov.:

AF XY:

0.0102

AC XY:

7388

AN XY:

727184

show subpopulations

African (AFR)

AF:

0.00185

AC:

AN:

33476

American (AMR)

AF:

0.00304

AC:

136

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00624

AC:

163

AN:

26134

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.000881

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00852

AC:

455

AN:

53396

Middle Eastern (MID)

AF:

0.000350

AC:

AN:

5718

European-Non Finnish (NFE)

AF:

0.0126

AC:

13977

AN:

1111996

Other (OTH)

AF:

0.00871

AC:

526

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

809

1617

2426

3234

4043

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

542

1084

1626

2168

2710

<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:

0.00680

AC:

1034

AN:

151950

Hom.:

Cov.:

AF XY:

0.00603

AC XY:

448

AN XY:

74248

show subpopulations

African (AFR)

AF:

0.00229

AC:

AN:

41444

American (AMR)

AF:

0.00342

AC:

AN:

15222

Ashkenazi Jewish (ASJ)

AF:

0.00548

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5172

South Asian (SAS)

AF:

0.000209

AC:

AN:

4778

European-Finnish (FIN)

AF:

0.00869

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0113

AC:

766

AN:

67968

Other (OTH)

AF:

0.00381

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

107

161

214

268

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:

0.00897

Hom.:

Bravo

AF:

0.00610

TwinsUK

AF:

0.0138

AC:

ALSPAC

AF:

0.0122

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.0108

AC:

ExAC

AF:

0.00708

AC:

860

Asia WGS

AF:

0.000577

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

0.060

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.40

CADD

Benign

7.5

(source)

DANN

Benign

0.58

DEOGEN2

Benign

0.025

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.0074

LIST_S2

Benign

0.69

MetaRNN

Benign

0.0037

MetaSVM

Benign

-0.69

MutationAssessor

Benign

-1.1

PhyloP100

0.21

PrimateAI

Benign

0.21

PROVEAN

Benign

0.66

REVEL

Benign

0.17

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0030

Vest4

0.11

MVP

0.52

MPC

0.24

ClinPred

0.0051

GERP RS

1.3

Varity_R

0.030

gMVP

0.28

Mutation Taster

=97/3

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