8-100162160-C-T

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.-2-119C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0132 in 770,450 control chromosomes in the GnomAD database, including 821 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0095 (120 hom., cov: 32)
  • Exomes 𝑓: 0.014 (701 hom.)
• Consequence: SPAG1 NM_003114.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.279

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=-0.91).
• BP6: Variant 8-100162160-C-T is Benign according to our data. Variant chr8-100162160-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1196738.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPAG1	NM_003114.5	c.-2-119C>T		intron_variant		ENST00000388798.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPAG1	ENST00000388798.7	c.-2-119C>T		intron_variant		1	NM_003114.5	P1
SPAG1	ENST00000251809.4	c.-2-119C>T		intron_variant		5		P1
SPAG1	ENST00000520508.5	c.-2-119C>T		intron_variant		5
SPAG1	ENST00000520643.5	c.-2-119C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.00947 AC: 1440 AN: 152104 Hom.: 117 Cov.: 32

Gnomad AFR AF: 0.000797

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00674

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.0545

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0105

GnomAD4 exome AF: 0.0141 AC: 8701 AN: 618228 Hom.: 701 AF XY: 0.0150 AC XY: 4860 AN XY: 324502

Gnomad4 AFR exome AF: 0.000292

Gnomad4 AMR exome AF: 0.00658

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.204

Gnomad4 SAS exome AF: 0.0430

Gnomad4 FIN exome AF: 0.0000461

Gnomad4 NFE exome AF: 0.000377

Gnomad4 OTH exome AF: 0.0161

GnomAD4 genome AF: 0.00951 AC: 1448 AN: 152222 Hom.: 120 Cov.: 32 AF XY: 0.0114 AC XY: 851 AN XY: 74410

Gnomad4 AFR AF: 0.000794

Gnomad4 AMR AF: 0.00673

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.0546

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.0156

Alfa AF: 0.00243 Hom.: 1

Bravo AF: 0.0107

Asia WGS AF: 0.111 AC: 384 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	4.2
Dann	Benign	0.33

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: rs77783647; hg19: chr8-101174388;