rs9895463

Positions:

• chr17-32985509-A-G
• chr17-32985509-A-T

Variant summary

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

The ENST00000580599.5(SPACA3):​c.-174+9565A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 151,976 control chromosomes in the GnomAD database, including 20,505 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 0.51 (20505 hom., cov: 32)
• Consequence: SPACA3 ENST00000580599.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.365

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPACA3	ENST00000580599.5	c.-174+9565A>G		intron_variant		1		ENSP00000463386	P2

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77914 AN: 151858 Hom.: 20493 Cov.: 32

Gnomad AFR AF: 0.620

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.488

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

GnomAD4 genome AF: 0.513 AC: 77946 AN: 151976 Hom.: 20505 Cov.: 32 AF XY: 0.511 AC XY: 37932 AN XY: 74296

Gnomad4 AFR AF: 0.620

Gnomad4 AMR AF: 0.486

Gnomad4 ASJ AF: 0.419

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.411

Gnomad4 FIN AF: 0.473

Gnomad4 NFE AF: 0.481

Gnomad4 OTH AF: 0.487

Alfa AF: 0.471 Hom.: 9021

Bravo AF: 0.519

Asia WGS AF: 0.423 AC: 1473 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.84
DANN	Benign	0.49

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9895463; hg19: chr17-31312527;