Genetic Variant NM_052961.4:c.217G>A (chr6-36012344-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

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

Publications

32 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:

LOC105375034 (HGNC:):

LOC105375034 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=0.0010611117).

BP6

Variant 6-36012344-C-T is Benign according to our data. Variant chr6-36012344-C-T is described in ClinVar as Benign. ClinVar VariationId 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

GnomAD2 exomes

AF:

0.234

AC:

55656

AN:

237844

AF XY:

0.229

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 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

African (AFR)

AF:

0.425

AC:

13820

AN:

32510

American (AMR)

AF:

0.196

AC:

8064

AN:

41078

Ashkenazi Jewish (ASJ)

AF:

0.322

AC:

8269

AN:

25698

East Asian (EAS)

AF:

0.107

AC:

4173

AN:

39048

South Asian (SAS)

AF:

0.183

AC:

15340

AN:

83852

European-Finnish (FIN)

AF:

0.254

AC:

13541

AN:

53304

Middle Eastern (MID)

AF:

0.270

AC:

1548

AN:

5728

European-Non Finnish (NFE)

AF:

0.237

AC:

262062

AN:

1107398

Other (OTH)

AF:

0.241

AC:

14403

AN:

59858

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

13161

26322

39483

52644

65805

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8860

17720

26580

35440

44300

<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:

0.289

AC:

43917

AN:

151964

Hom.:

6875

Cov.:

AF XY:

0.286

AC XY:

21204

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.426

AC:

17656

AN:

41414

American (AMR)

AF:

0.233

AC:

3553

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.322

AC:

1117

AN:

3468

East Asian (EAS)

AF:

0.104

AC:

540

AN:

5176

South Asian (SAS)

AF:

0.183

AC:

879

AN:

4808

European-Finnish (FIN)

AF:

0.238

AC:

2509

AN:

10564

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.246

AC:

16739

AN:

67942

Other (OTH)

AF:

0.321

AC:

679

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1559

3118

4676

6235

7794

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

428

856

1284

1712

2140

<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:

0.258

Hom.:

17943

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

(source)

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;.

PhyloP100

-0.025

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

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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