8-100161958-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003114.5(SPAG1):c.-2-321A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 152,076 control chromosomes in the GnomAD database, including 28,951 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.61 (28951 hom., cov: 32)
• Consequence: SPAG1 NM_003114.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.80

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 8-100161958-A-C is Benign according to our data. Variant chr8-100161958-A-C is described in ClinVar as [Benign]. Clinvar id is 1241493.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPAG1	NM_003114.5	c.-2-321A>C		intron_variant		ENST00000388798.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPAG1	ENST00000388798.7	c.-2-321A>C		intron_variant		1	NM_003114.5	P1
SPAG1	ENST00000251809.4	c.-2-321A>C		intron_variant		5		P1
SPAG1	ENST00000520508.5	c.-2-321A>C		intron_variant		5
SPAG1	ENST00000520643.5	c.-2-321A>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93411 AN: 151958 Hom.: 28934 Cov.: 32

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.679

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.583

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.602

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.602

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.615 AC: 93472 AN: 152076 Hom.: 28951 Cov.: 32 AF XY: 0.615 AC XY: 45722 AN XY: 74348

Gnomad4 AFR AF: 0.684

Gnomad4 AMR AF: 0.679

Gnomad4 ASJ AF: 0.576

Gnomad4 EAS AF: 0.688

Gnomad4 SAS AF: 0.582

Gnomad4 FIN AF: 0.579

Gnomad4 NFE AF: 0.564

Gnomad4 OTH AF: 0.600

Alfa AF: 0.595 Hom.: 4628

Bravo AF: 0.626

Asia WGS AF: 0.637 AC: 2216 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 13, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.77
Dann	Benign	0.53

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

Other links and lift over

dbSNP: rs2514692; hg19: chr8-101174186;