8-100165529-C-A

Position:

• chr8-100165529-C-A

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.141-285C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 369,032 control chromosomes in the GnomAD database, including 25,300 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (10981 hom., cov: 32)
  • Exomes 𝑓: 0.35 (14319 hom.)
• Consequence: SPAG1 NM_003114.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.976

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]

UFM1P3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 8-100165529-C-A is Benign according to our data. Variant chr8-100165529-C-A is described in ClinVar as [Benign]. Clinvar id is 1239077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPAG1	NM_003114.5	c.141-285C>A		intron_variant		ENST00000388798.7	NP_003105.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPAG1	ENST00000388798.7	c.141-285C>A		intron_variant		1	NM_003114.5	ENSP00000373450.3
SPAG1	ENST00000251809.4	c.141-285C>A		intron_variant		5		ENSP00000251809.3
SPAG1	ENST00000520508.5	c.141-285C>A		intron_variant		5		ENSP00000428070.1
SPAG1	ENST00000520643.5	c.141-285C>A		intron_variant		2		ENSP00000427716.1

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57098 AN: 151660 Hom.: 10973 Cov.: 32

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.362

GnomAD4 exome AF: 0.353 AC: 76714 AN: 217254 Hom.: 14319 AF XY: 0.347 AC XY: 40825 AN XY: 117566

Gnomad4 AFR exome AF: 0.386

Gnomad4 AMR exome AF: 0.473

Gnomad4 ASJ exome AF: 0.328

Gnomad4 EAS exome AF: 0.499

Gnomad4 SAS exome AF: 0.294

Gnomad4 FIN exome AF: 0.331

Gnomad4 NFE exome AF: 0.350

Gnomad4 OTH exome AF: 0.355

GnomAD4 genome AF: 0.376 AC: 57129 AN: 151778 Hom.: 10981 Cov.: 32 AF XY: 0.376 AC XY: 27907 AN XY: 74180

Gnomad4 AFR AF: 0.390

Gnomad4 AMR AF: 0.468

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.510

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.331

Gnomad4 NFE AF: 0.352

Gnomad4 OTH AF: 0.362

Alfa AF: 0.218 Hom.: 457

Bravo AF: 0.392

Asia WGS AF: 0.404 AC: 1406 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 31, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.54
DANN	Benign	0.55

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: rs2248768; hg19: chr8-101177757;