rs28958

Positions:

• chr17-32997639-T-C
• chr17-32997639-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000269053.8(SPACA3):​c.582-73T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 1,557,224 control chromosomes in the GnomAD database, including 136,857 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.48 (19042 hom., cov: 31)
  • Exomes 𝑓: 0.40 (117815 hom.)
• Consequence: SPACA3 ENST00000269053.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.382

Genes affected

SPACA3 (HGNC:16260): (sperm acrosome associated 3) The protein encoded by this gene is a sperm surface protein that may be involved in adhesion to the egg prior to fertilization. While the encoded protein has significant similarity to lysozyme at the amino acid level, it has no detectable bacteriocidal activity. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPACA3	NM_173847.5	c.582-73T>C		intron_variant		ENST00000269053.8	NP_776246.1
SPACA3	NM_001317225.2	c.306-73T>C		intron_variant			NP_001304154.1
SPACA3	NM_001317226.2	c.273-73T>C		intron_variant			NP_001304155.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPACA3	ENST00000269053.8	c.582-73T>C		intron_variant		1	NM_173847.5	ENSP00000269053	A2
SPACA3	ENST00000580599.5	c.375-73T>C		intron_variant		1		ENSP00000463386	P2
SPACA3	ENST00000394637.2	n.725-73T>C		intron_variant, non_coding_transcript_variant		1
SPACA3	ENST00000394638.1	c.273-73T>C		intron_variant		3		ENSP00000378134

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72467 AN: 151798 Hom.: 19004 Cov.: 31

Gnomad AFR AF: 0.709

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.452

GnomAD4 exome AF: 0.402 AC: 564885 AN: 1405308 Hom.: 117815 Cov.: 24 AF XY: 0.405 AC XY: 284846 AN XY: 702510

Gnomad4 AFR exome AF: 0.720

Gnomad4 AMR exome AF: 0.269

Gnomad4 ASJ exome AF: 0.336

Gnomad4 EAS exome AF: 0.458

Gnomad4 SAS exome AF: 0.548

Gnomad4 FIN exome AF: 0.411

Gnomad4 NFE exome AF: 0.384

Gnomad4 OTH exome AF: 0.420

GnomAD4 genome AF: 0.478 AC: 72550 AN: 151916 Hom.: 19042 Cov.: 31 AF XY: 0.479 AC XY: 35573 AN XY: 74264

Gnomad4 AFR AF: 0.709

Gnomad4 AMR AF: 0.342

Gnomad4 ASJ AF: 0.341

Gnomad4 EAS AF: 0.440

Gnomad4 SAS AF: 0.556

Gnomad4 FIN AF: 0.417

Gnomad4 NFE AF: 0.382

Gnomad4 OTH AF: 0.457

Alfa AF: 0.394 Hom.: 15379

Bravo AF: 0.476

Asia WGS AF: 0.543 AC: 1885 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.3
DANN	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs28958; hg19: chr17-31324657;