8-100240956-G-A

Position:

chr8-100240956-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000388798.7(SPAG1):c.2715G>A(p.Ser905=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 1,611,486 control chromosomes in the GnomAD database, including 104,519 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 7844 hom., cov: 30)

Exomes 𝑓: 0.36 ( 96675 hom. )

Consequence

SPAG1
ENST00000388798.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.649

Variant links:

Genes affected

SPAG1 (HGNC:11212): (sperm associated antigen 1) 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 agglutinating antibodies from an infertile woman. Furthermore, immunization of female rats with the recombinant human protein reduced fertility. This protein localizes to the plasma membrane of germ cells in the testis and to the post-acrosomal plasma membrane of mature spermatozoa. Recombinant polypeptide binds GTP and exhibits GTPase activity. Thus, this protein may regulate GTP signal transduction pathways involved in spermatogenesis and fertilization. Two transcript variants of this gene encode the same protein. [provided by RefSeq, Jul 2008]

SPAG1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 8-100240956-G-A is Benign according to our data. Variant chr8-100240956-G-A is described in ClinVar as [Benign]. Clinvar id is 262803.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.649 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPAG1	NM_003114.5 linkuse as main transcript	c.2715G>A	p.Ser905=	synonymous_variant	19/19	ENST00000388798.7	NP_003105.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPAG1	ENST00000388798.7 linkuse as main transcript	c.2715G>A	p.Ser905=	synonymous_variant	19/19	1	NM_003114.5	ENSP00000373450	P1	Q07617-1
SPAG1	ENST00000251809.4 linkuse as main transcript	c.2715G>A	p.Ser905=	synonymous_variant	19/19	5		ENSP00000251809	P1	Q07617-1
SPAG1	ENST00000519409.1 linkuse as main transcript	n.213+185G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.293

AC:

44144

AN:

150532

Hom.:

7841

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0809

Gnomad AMI

AF:

0.464

Gnomad AMR

AF:

0.426

Gnomad ASJ

AF:

0.347

Gnomad EAS

AF:

0.496

Gnomad SAS

AF:

0.297

Gnomad FIN

AF:

0.340

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.364

Gnomad OTH

AF:

0.300

GnomAD3 exomes

AF:

0.363

AC:

90876

AN:

250508

Hom.:

18052

AF XY:

0.360

AC XY:

48754

AN XY:

135464

show subpopulations

Gnomad AFR exome

AF:

0.0725

Gnomad AMR exome

AF:

0.490

Gnomad ASJ exome

AF:

0.340

Gnomad EAS exome

AF:

0.485

Gnomad SAS exome

AF:

0.299

Gnomad FIN exome

AF:

0.339

Gnomad NFE exome

AF:

0.370

Gnomad OTH exome

AF:

0.350

GnomAD4 exome

AF:

0.358

AC:

523517

AN:

1460846

Hom.:

96675

Cov.:

AF XY:

0.357

AC XY:

259431

AN XY:

726734

show subpopulations

Gnomad4 AFR exome

AF:

0.0708

Gnomad4 AMR exome

AF:

0.479

Gnomad4 ASJ exome

AF:

0.339

Gnomad4 EAS exome

AF:

0.490

Gnomad4 SAS exome

AF:

0.299

Gnomad4 FIN exome

AF:

0.330

Gnomad4 NFE exome

AF:

0.365

Gnomad4 OTH exome

AF:

0.343

GnomAD4 genome

AF:

0.293

AC:

44153

AN:

150640

Hom.:

7844

Cov.:

AF XY:

0.297

AC XY:

21850

AN XY:

73530

show subpopulations

Gnomad4 AFR

AF:

0.0809

Gnomad4 AMR

AF:

0.426

Gnomad4 ASJ

AF:

0.347

Gnomad4 EAS

AF:

0.496

Gnomad4 SAS

AF:

0.299

Gnomad4 FIN

AF:

0.340

Gnomad4 NFE

AF:

0.364

Gnomad4 OTH

AF:

0.300

Alfa

AF:

0.349

Hom.:

14744

Bravo

AF:

0.291

Asia WGS

AF:

0.362

AC:

1256

AN:

3474

EpiCase

AF:

0.358

EpiControl

AF:

0.363

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Primary ciliary dyskinesia 28

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 17, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Primary ciliary dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 07, 2016

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.1

DANN

Benign

0.37

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over