rs12462673

Positions:

• chr19-51695401-A-G

Variant summary

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

The NM_001316972.2(SPACA6):​c.292+846A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0488 in 152,296 control chromosomes in the GnomAD database, including 262 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 0.049 (262 hom., cov: 32)
• Consequence: SPACA6 NM_001316972.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.33

Genes affected

SPACA6 (HGNC:27113): (sperm acrosome associated 6) Predicted to be involved in fusion of sperm to egg plasma membrane involved in single fertilization. Predicted to be located in acrosomal vesicle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPACA6	NM_001316972.2	c.292+846A>G		intron_variant		ENST00000637797.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPACA6	ENST00000637797.2	c.292+846A>G		intron_variant		1	NM_001316972.2	P2

Frequencies

GnomAD3 genomes AF: 0.0488 AC: 7428 AN: 152178 Hom.: 262 Cov.: 32

Gnomad AFR AF: 0.0738

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0687

Gnomad ASJ AF: 0.0323

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.0179

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0260

Gnomad OTH AF: 0.0474

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

GnomAD4 genome AF: 0.0488 AC: 7434 AN: 152296 Hom.: 262 Cov.: 32 AF XY: 0.0511 AC XY: 3804 AN XY: 74462

Gnomad4 AFR AF: 0.0737

Gnomad4 AMR AF: 0.0690

Gnomad4 ASJ AF: 0.0323

Gnomad4 EAS AF: 0.103

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.0179

Gnomad4 NFE AF: 0.0260

Gnomad4 OTH AF: 0.0469

Alfa AF: 0.0422 Hom.: 45

Bravo AF: 0.0533

Asia WGS AF: 0.122 AC: 425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.14
DANN	Benign	0.39

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12462673; hg19: chr19-52198654;