8-100162198-G-A

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.-2-81G>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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00500

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=-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_single_submitter, 1 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	UniProt
SPAG1	NM_003114.5	c.-2-81G>A		intron_variant		ENST00000388798.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPAG1	ENST00000388798.7	c.-2-81G>A		intron_variant		1	NM_003114.5	P1
SPAG1	ENST00000251809.4	c.-2-81G>A		intron_variant		5		P1
SPAG1	ENST00000520508.5	c.-2-81G>A		intron_variant		5
SPAG1	ENST00000520643.5	c.-2-81G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32758 AN: 151936 Hom.: 3669 Cov.: 32

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

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.: 32 AF XY: 0.216 AC XY: 16090 AN XY: 74328

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 20, 2019

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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

Other links and lift over

dbSNP: rs16898015; hg19: chr8-101174426; COSMIC: COSV52562085; COSMIC: COSV52562085;