Variant 10-22386928-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_012443.4(SPAG6):c.647A>G(p.Gln216Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0384 in 1,613,474 control chromosomes in the GnomAD database, including 10,837 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.16 ( 5538 hom., cov: 32)

Exomes 𝑓: 0.026 ( 5299 hom. )

Consequence

SPAG6
NM_012443.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.18

Variant links:

Genes affected

SPAG6 (HGNC:11215): (sperm associated antigen 6) The correlation of anti-sperm antibodies with cases of unexplained infertility implicates a role for these antibodies in blocking fertilization. Improved diagnosis and treatment of immunologic infertility, as well as identification of proteins for targeted contraception, are dependent on the identification and characterization of relevant sperm antigens. The protein expressed by this gene is recognized by anti-sperm antibodies from an infertile man. This protein localizes to the tail of permeabilized human sperm and contains eight contiguous armadillo repeats, a motif known to mediate protein-protein interactions. Studies in mice suggest that this protein is involved in sperm flagellar motility and maintenance of the structural integrity of mature sperm. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

SPAG6 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.201863E-4).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPAG6	NM_012443.4 linkuse as main transcript	c.647A>G	p.Gln216Arg	missense_variant	5/11	ENST00000376624.8	NP_036575.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPAG6	ENST00000376624.8 linkuse as main transcript	c.647A>G	p.Gln216Arg	missense_variant	5/11	1	NM_012443.4	ENSP00000365811	P1	O75602-1
	ENST00000422675.1 linkuse as main transcript	n.250+25507A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.156

AC:

23700

AN:

152062

Hom.:

5502

Cov.:

show subpopulations

Gnomad AFR

AF:

0.509

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0768

Gnomad ASJ

AF:

0.0507

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.0108

Gnomad FIN

AF:

0.00480

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0140

Gnomad OTH

AF:

0.118

GnomAD3 exomes

AF:

0.0505

AC:

12679

AN:

250868

Hom.:

2317

AF XY:

0.0404

AC XY:

5472

AN XY:

135564

show subpopulations

Gnomad AFR exome

AF:

0.521

Gnomad AMR exome

AF:

0.0406

Gnomad ASJ exome

AF:

0.0456

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00895

Gnomad FIN exome

AF:

0.00619

Gnomad NFE exome

AF:

0.0150

Gnomad OTH exome

AF:

0.0407

GnomAD4 exome

AF:

0.0261

AC:

38171

AN:

1461294

Hom.:

5299

Cov.:

AF XY:

0.0242

AC XY:

17615

AN XY:

726942

show subpopulations

Gnomad4 AFR exome

AF:

0.534

Gnomad4 AMR exome

AF:

0.0457

Gnomad4 ASJ exome

AF:

0.0437

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.00914

Gnomad4 FIN exome

AF:

0.00652

Gnomad4 NFE exome

AF:

0.0112

Gnomad4 OTH exome

AF:

0.0506

GnomAD4 genome

AF:

0.156

AC:

23787

AN:

152180

Hom.:

5538

Cov.:

AF XY:

0.150

AC XY:

11190

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.510

Gnomad4 AMR

AF:

0.0767

Gnomad4 ASJ

AF:

0.0507

Gnomad4 EAS

AF:

0.000771

Gnomad4 SAS

AF:

0.00973

Gnomad4 FIN

AF:

0.00480

Gnomad4 NFE

AF:

0.0140

Gnomad4 OTH

AF:

0.117

Alfa

AF:

0.0459

Hom.:

2023

Bravo

AF:

0.179

TwinsUK

AF:

0.0111

AC:

ALSPAC

AF:

0.00778

AC:

ESP6500AA

AF:

0.509

AC:

2243

ESP6500EA

AF:

0.0160

AC:

138

ExAC

AF:

0.0595

AC:

7224

Asia WGS

AF:

0.0510

AC:

179

AN:

3478

EpiCase

AF:

0.0190

EpiControl

AF:

0.0176

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.65

DEOGEN2

Benign

0.012

T;T;.;.

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.92

D;D;D;D

MetaRNN

Benign

0.00062

T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.6

.;L;L;.

MutationTaster

Benign

6.6e-7

P;P;P;P;P

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.65

.;N;N;N

REVEL

Benign

0.19

Sift

Benign

0.43

.;T;T;T

Sift4G

Benign

0.46

T;T;T;T

Polyphen

0.0010, 0.0020

.;B;B;.

Vest4

0.31

MPC

0.30

ClinPred

0.020

GERP RS

4.5

Varity_R

0.36

gMVP

0.48

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over