Variant 8-100162198-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_003114.5(SPAG1):c.-2-81G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 1,148,662 control chromosomes in the GnomAD database, including 24,104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 3673 hom., cov: 32)

Exomes 𝑓: 0.20 ( 20431 hom. )

Consequence

SPAG1
NM_003114.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.00500

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 (BayesDel_noAF=-0.93).

BP6

Variant 8-100162198-G-A is Benign according to our data. Variant chr8-100162198-G-A is described in ClinVar as [Benign]. Clinvar id is 1248919.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 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.-2-81G>A		intron_variant		ENST00000388798.7	NP_003105.2	Q07617-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
SPAG1	ENST00000388798.7 linkuse as main transcript	c.-2-81G>A	intron_variant	1	NM_003114.5	ENSP00000373450.3	Q07617-1
SPAG1	ENST00000251809.4 linkuse as main transcript	c.-2-81G>A	intron_variant	5		ENSP00000251809.3	Q07617-1
SPAG1	ENST00000520508.5 linkuse as main transcript	c.-2-81G>A	intron_variant	5		ENSP00000428070.1	Q07617-2
SPAG1	ENST00000520643.5 linkuse as main transcript	c.-2-81G>A	intron_variant	2		ENSP00000427716.1	Q07617-2

Frequencies

GnomAD3 genomes

AF:

0.216

AC:

32758

AN:

151936

Hom.:

3669

Cov.:

show subpopulations

Gnomad AFR

AF:

0.266

Gnomad AMI

AF:

0.0954

Gnomad AMR

AF:

0.192

Gnomad ASJ

AF:

0.203

Gnomad EAS

AF:

0.173

Gnomad SAS

AF:

0.261

Gnomad FIN

AF:

0.231

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.190

Gnomad OTH

AF:

0.218

GnomAD4 exome

AF:

0.199

AC:

198517

AN:

996608

Hom.:

20431

AF XY:

0.201

AC XY:

101161

AN XY:

504228

show subpopulations

Gnomad4 AFR exome

AF:

0.265

Gnomad4 AMR exome

AF:

0.208

Gnomad4 ASJ exome

AF:

0.195

Gnomad4 EAS exome

AF:

0.203

Gnomad4 SAS exome

AF:

0.278

Gnomad4 FIN exome

AF:

0.239

Gnomad4 NFE exome

AF:

0.188

Gnomad4 OTH exome

AF:

0.202

GnomAD4 genome

AF:

0.216

AC:

32793

AN:

152054

Hom.:

3673

Cov.:

AF XY:

0.216

AC XY:

16090

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.266

Gnomad4 AMR

AF:

0.192

Gnomad4 ASJ

AF:

0.203

Gnomad4 EAS

AF:

0.173

Gnomad4 SAS

AF:

0.260

Gnomad4 FIN

AF:

0.231

Gnomad4 NFE

AF:

0.190

Gnomad4 OTH

AF:

0.217

Alfa

AF:

0.184

Hom.:

3049

Bravo

AF:

0.213

Asia WGS

AF:

0.217

AC:

754

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 20, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

3.7

DANN

Benign

0.41

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