rs6511

Positions:

chr8-100240452-T-C

Variant summary

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

The NM_003114.5(SPAG1):c.2330T>C(p.Met777Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 1,613,048 control chromosomes in the GnomAD database, including 302,826 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 0.64 ( 31128 hom., cov: 30)

Exomes 𝑓: 0.61 ( 271698 hom. )

Consequence

SPAG1
NM_003114.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.210

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=1.8907637E-6).

BP6

Variant 8-100240452-T-C is Benign according to our data. Variant chr8-100240452-T-C is described in ClinVar as [Benign]. Clinvar id is 262802.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.694 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.2330T>C	p.Met777Thr	missense_variant	18/19	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.2330T>C	p.Met777Thr	missense_variant	18/19	1	NM_003114.5	ENSP00000373450	P1	Q07617-1
SPAG1	ENST00000251809.4 linkuse as main transcript	c.2330T>C	p.Met777Thr	missense_variant	18/19	5		ENSP00000251809	P1	Q07617-1
SPAG1	ENST00000519424.1 linkuse as main transcript	n.582T>C		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.638

AC:

96826

AN:

151754

Hom.:

31099

Cov.:

show subpopulations

Gnomad AFR

AF:

0.701

Gnomad AMI

AF:

0.679

Gnomad AMR

AF:

0.696

Gnomad ASJ

AF:

0.582

Gnomad EAS

AF:

0.519

Gnomad SAS

AF:

0.542

Gnomad FIN

AF:

0.610

Gnomad MID

AF:

0.620

Gnomad NFE

AF:

0.610

Gnomad OTH

AF:

0.629

GnomAD3 exomes

AF:

0.618

AC:

155095

AN:

250818

Hom.:

48541

AF XY:

0.611

AC XY:

82885

AN XY:

135608

show subpopulations

Gnomad AFR exome

AF:

0.698

Gnomad AMR exome

AF:

0.720

Gnomad ASJ exome

AF:

0.575

Gnomad EAS exome

AF:

0.504

Gnomad SAS exome

AF:

0.560

Gnomad FIN exome

AF:

0.617

Gnomad NFE exome

AF:

0.615

Gnomad OTH exome

AF:

0.614

GnomAD4 exome

AF:

0.608

AC:

888959

AN:

1461176

Hom.:

271698

Cov.:

AF XY:

0.606

AC XY:

440419

AN XY:

726916

show subpopulations

Gnomad4 AFR exome

AF:

0.703

Gnomad4 AMR exome

AF:

0.716

Gnomad4 ASJ exome

AF:

0.575

Gnomad4 EAS exome

AF:

0.502

Gnomad4 SAS exome

AF:

0.563

Gnomad4 FIN exome

AF:

0.615

Gnomad4 NFE exome

AF:

0.609

Gnomad4 OTH exome

AF:

0.606

GnomAD4 genome

AF:

0.638

AC:

96907

AN:

151872

Hom.:

31128

Cov.:

AF XY:

0.638

AC XY:

47319

AN XY:

74214

show subpopulations

Gnomad4 AFR

AF:

0.701

Gnomad4 AMR

AF:

0.697

Gnomad4 ASJ

AF:

0.582

Gnomad4 EAS

AF:

0.519

Gnomad4 SAS

AF:

0.542

Gnomad4 FIN

AF:

0.610

Gnomad4 NFE

AF:

0.610

Gnomad4 OTH

AF:

0.625

Alfa

AF:

0.612

Hom.:

55379

Bravo

AF:

0.647

TwinsUK

AF:

0.604

AC:

2240

ALSPAC

AF:

0.602

AC:

2320

ESP6500AA

AF:

0.692

AC:

3051

ESP6500EA

AF:

0.609

AC:

5241

ExAC

AF:

0.617

AC:

74887

Asia WGS

AF:

0.518

AC:

1805

AN:

3478

EpiCase

AF:

0.611

EpiControl

AF:

0.615

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
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 -

Primary ciliary dyskinesia 28

Benign:2

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

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.056

DANN

Benign

0.16

DEOGEN2

Benign

0.0077

T;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0084

LIST_S2

Benign

0.089

T;.

MetaRNN

Benign

0.0000019

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-1.6

N;N

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.24

PROVEAN

Benign

2.3

N;N

REVEL

Benign

0.041

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.011

MPC

0.17

ClinPred

0.00030

GERP RS

-3.7

Varity_R

0.027

gMVP

0.19

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