rs12462673

Variant names:

• chr19-51695401-A-G
• rs12462673
• NM_001316972.2:c.292+846A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SPACA6	NM_001316972.2	c.292+846A>G		intron_variant	Intron 2 of 8	ENST00000637797.2	NP_001303901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPACA6	ENST00000637797.2	c.292+846A>G		intron_variant	Intron 2 of 8	1	NM_001316972.2	ENSP00000490829.1

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

African (AFR) AF: 0.0737 AC: 3066 AN: 41576

American (AMR) AF: 0.0690 AC: 1056 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0323 AC: 112 AN: 3468

East Asian (EAS) AF: 0.103 AC: 532 AN: 5162

South Asian (SAS) AF: 0.117 AC: 565 AN: 4826

European-Finnish (FIN) AF: 0.0179 AC: 190 AN: 10622

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0260 AC: 1769 AN: 68018

Other (OTH) AF: 0.0469 AC: 99 AN: 2112

Alfa AF: 0.0431 Hom.: 46

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
PhyloP100		-2.3

Splicing

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

Other links and lift over

dbSNP: rs12462673; hg19: chr19-52198654;