rs17335870

Positions:

chr8-100194163-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003114.5(SPAG1):c.991G>A(p.Glu331Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 1,596,798 control chromosomes in the GnomAD database, including 32,652 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2459 hom., cov: 33)

Exomes 𝑓: 0.20 ( 30193 hom. )

Consequence

SPAG1
NM_003114.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.411

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002596289).

BP6

Variant 8-100194163-G-A is Benign according to our data. Variant chr8-100194163-G-A is described in ClinVar as [Benign]. Clinvar id is 262805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.217 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.991G>A	p.Glu331Lys	missense_variant	10/19	ENST00000388798.7	NP_003105.2	Q07617-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SPAG1	ENST00000388798.7 linkuse as main transcript	c.991G>A	p.Glu331Lys	missense_variant	10/19	1	NM_003114.5	ENSP00000373450.3	Q07617-1
SPAG1	ENST00000251809.4 linkuse as main transcript	c.991G>A	p.Glu331Lys	missense_variant	10/19	5		ENSP00000251809.3	Q07617-1
SPAG1	ENST00000520508.5 linkuse as main transcript	c.991G>A	p.Glu331Lys	missense_variant	10/10	5		ENSP00000428070.1	Q07617-2
SPAG1	ENST00000520643.5 linkuse as main transcript	c.991G>A	p.Glu331Lys	missense_variant	10/10	2		ENSP00000427716.1	Q07617-2

Frequencies

GnomAD3 genomes

AF:

0.168

AC:

25513

AN:

152040

Hom.:

2462

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0746

Gnomad AMI

AF:

0.145

Gnomad AMR

AF:

0.180

Gnomad ASJ

AF:

0.228

Gnomad EAS

AF:

0.0723

Gnomad SAS

AF:

0.229

Gnomad FIN

AF:

0.248

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.209

Gnomad OTH

AF:

0.187

GnomAD3 exomes

AF:

0.188

AC:

45554

AN:

242126

Hom.:

4761

AF XY:

0.193

AC XY:

25274

AN XY:

130742

show subpopulations

Gnomad AFR exome

AF:

0.0689

Gnomad AMR exome

AF:

0.195

Gnomad ASJ exome

AF:

0.212

Gnomad EAS exome

AF:

0.0522

Gnomad SAS exome

AF:

0.230

Gnomad FIN exome

AF:

0.245

Gnomad NFE exome

AF:

0.201

Gnomad OTH exome

AF:

0.204

GnomAD4 exome

AF:

0.200

AC:

288370

AN:

1444638

Hom.:

30193

Cov.:

AF XY:

0.201

AC XY:

144427

AN XY:

718100

show subpopulations

Gnomad4 AFR exome

AF:

0.0639

Gnomad4 AMR exome

AF:

0.195

Gnomad4 ASJ exome

AF:

0.221

Gnomad4 EAS exome

AF:

0.0782

Gnomad4 SAS exome

AF:

0.238

Gnomad4 FIN exome

AF:

0.253

Gnomad4 NFE exome

AF:

0.202

Gnomad4 OTH exome

AF:

0.197

GnomAD4 genome

AF:

0.168

AC:

25508

AN:

152160

Hom.:

2459

Cov.:

AF XY:

0.169

AC XY:

12592

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.0746

Gnomad4 AMR

AF:

0.180

Gnomad4 ASJ

AF:

0.228

Gnomad4 EAS

AF:

0.0723

Gnomad4 SAS

AF:

0.228

Gnomad4 FIN

AF:

0.248

Gnomad4 NFE

AF:

0.209

Gnomad4 OTH

AF:

0.184

Alfa

AF:

0.198

Hom.:

6614

Bravo

AF:

0.157

TwinsUK

AF:

0.198

AC:

736

ALSPAC

AF:

0.200

AC:

770

ESP6500AA

AF:

0.0756

AC:

333

ESP6500EA

AF:

0.200

AC:

1720

ExAC

AF:

0.195

AC:

23658

Asia WGS

AF:

0.149

AC:

520

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 27, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Primary ciliary dyskinesia 28

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Primary ciliary dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 12, 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

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

6.0

DANN

Benign

0.21

DEOGEN2

Benign

0.0091

.;T;.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.14

.;T;T;.

MetaRNN

Benign

0.0026

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.5

N;N;N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

1.0

N;N;N;N

REVEL

Benign

0.073

Sift

Benign

0.94

T;T;T;T

Sift4G

Benign

0.84

T;T;T;T

Polyphen

0.0

.;B;.;B

Vest4

0.016

MPC

0.17

ClinPred

0.00022

GERP RS

-1.6

Varity_R

0.029

gMVP

0.11

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