rs3802149

Positions:

• chr8-100191509-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003114.5(SPAG1):​c.939+13T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,548,334 control chromosomes in the GnomAD database, including 32,478 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2456 hom., cov: 32)
  • Exomes 𝑓: 0.20 (30022 hom.)
• Consequence: SPAG1 NM_003114.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.127

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 8-100191509-T-C is Benign according to our data. Variant chr8-100191509-T-C is described in ClinVar as [Benign]. Clinvar id is 262804.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	c.939+13T>C		intron_variant		ENST00000388798.7	NP_003105.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPAG1	ENST00000388798.7	c.939+13T>C		intron_variant		1	NM_003114.5	ENSP00000373450	P1
SPAG1	ENST00000251809.4	c.939+13T>C		intron_variant		5		ENSP00000251809	P1
SPAG1	ENST00000520508.5	c.939+13T>C		intron_variant		5		ENSP00000428070
SPAG1	ENST00000520643.5	c.939+13T>C		intron_variant		2		ENSP00000427716

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25513 AN: 152082 Hom.: 2459 Cov.: 32

Gnomad AFR AF: 0.0747

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.0722

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.187

GnomAD3 exomes AF: 0.199 AC: 48737 AN: 245260 Hom.: 5313 AF XY: 0.204 AC XY: 27007 AN XY: 132620

Gnomad AFR exome AF: 0.0716

Gnomad AMR exome AF: 0.217

Gnomad ASJ exome AF: 0.225

Gnomad EAS exome AF: 0.0562

Gnomad SAS exome AF: 0.250

Gnomad FIN exome AF: 0.249

Gnomad NFE exome AF: 0.208

Gnomad OTH exome AF: 0.218

GnomAD4 exome AF: 0.203 AC: 283893 AN: 1396134 Hom.: 30022 Cov.: 22 AF XY: 0.205 AC XY: 142912 AN XY: 698032

Gnomad4 AFR exome AF: 0.0666

Gnomad4 AMR exome AF: 0.211

Gnomad4 ASJ exome AF: 0.227

Gnomad4 EAS exome AF: 0.0795

Gnomad4 SAS exome AF: 0.247

Gnomad4 FIN exome AF: 0.256

Gnomad4 NFE exome AF: 0.205

Gnomad4 OTH exome AF: 0.200

GnomAD4 genome AF: 0.168 AC: 25508 AN: 152200 Hom.: 2456 Cov.: 32 AF XY: 0.169 AC XY: 12589 AN XY: 74404

Gnomad4 AFR AF: 0.0747

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.228

Gnomad4 EAS AF: 0.0722

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.247

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.185

Alfa AF: 0.206 Hom.: 3647

Bravo AF: 0.157

Asia WGS AF: 0.150 AC: 522 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.0
DANN	Benign	0.65

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: rs3802149; hg19: chr8-101203737;