8-100162715-C-T

Position:

• chr8-100162715-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.140+295C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,090 control chromosomes in the GnomAD database, including 2,235 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.17 (2235 hom., cov: 32)
• Consequence: SPAG1 NM_003114.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.60

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 8-100162715-C-T is Benign according to our data. Variant chr8-100162715-C-T is described in ClinVar as [Benign]. Clinvar id is 1181021.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPAG1	NM_003114.5	c.140+295C>T		intron_variant		ENST00000388798.7	NP_003105.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPAG1	ENST00000388798.7	c.140+295C>T		intron_variant		1	NM_003114.5	ENSP00000373450.3
SPAG1	ENST00000251809.4	c.140+295C>T		intron_variant		5		ENSP00000251809.3
SPAG1	ENST00000520508.5	c.140+295C>T		intron_variant		5		ENSP00000428070.1
SPAG1	ENST00000520643.5	c.140+295C>T		intron_variant		2		ENSP00000427716.1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25383 AN: 151972 Hom.: 2237 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.0716

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.167 AC: 25389 AN: 152090 Hom.: 2235 Cov.: 32 AF XY: 0.168 AC XY: 12471 AN XY: 74360

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.0716

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.231

Gnomad4 NFE AF: 0.189

Gnomad4 OTH AF: 0.177

Alfa AF: 0.188 Hom.: 342

Bravo AF: 0.159

Asia WGS AF: 0.141 AC: 491 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

Nov 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.78
DANN	Benign	0.31

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: rs56321830; hg19: chr8-101174943;