19-51693156-G-A

Position:

• chr19-51693156-G-A

Variant summary

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

The NM_001316994.2(SPACA6):​c.92-1322G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0251 in 445,190 control chromosomes in the GnomAD database, including 267 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 0.022 (72 hom., cov: 32)
  • Exomes 𝑓: 0.027 (195 hom.)
• Consequence: SPACA6 NM_001316994.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00

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]

SPACA6-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPACA6	NM_001316994.2	c.92-1322G>A		intron_variant			NP_001303923.1
SPACA6	XM_017026300.3	c.-41-1322G>A		intron_variant			XP_016881789.1
SPACA6-AS1	NR_108100.1	n.301C>T		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPACA6	ENST00000710615.1	c.-41-1322G>A		intron_variant				ENSP00000518379.1
SPACA6	ENST00000646845.1	c.368-1322G>A		intron_variant				ENSP00000496692.1
SPACA6-AS1	ENST00000602324.1	n.301C>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.0223 AC: 3381 AN: 151902 Hom.: 71 Cov.: 32

Gnomad AFR AF: 0.00561

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0120

Gnomad ASJ AF: 0.0135

Gnomad EAS AF: 0.0990

Gnomad SAS AF: 0.00787

Gnomad FIN AF: 0.0348

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0287

Gnomad OTH AF: 0.0129

GnomAD4 exome AF: 0.0265 AC: 7777 AN: 293170 Hom.: 195 Cov.: 0 AF XY: 0.0249 AC XY: 3919 AN XY: 157076

Gnomad4 AFR exome AF: 0.00432

Gnomad4 AMR exome AF: 0.00577

Gnomad4 ASJ exome AF: 0.0124

Gnomad4 EAS exome AF: 0.103

Gnomad4 SAS exome AF: 0.00954

Gnomad4 FIN exome AF: 0.0315

Gnomad4 NFE exome AF: 0.0285

Gnomad4 OTH exome AF: 0.0225

GnomAD4 genome AF: 0.0223 AC: 3389 AN: 152020 Hom.: 72 Cov.: 32 AF XY: 0.0226 AC XY: 1677 AN XY: 74312

Gnomad4 AFR AF: 0.00560

Gnomad4 AMR AF: 0.0120

Gnomad4 ASJ AF: 0.0135

Gnomad4 EAS AF: 0.0986

Gnomad4 SAS AF: 0.00808

Gnomad4 FIN AF: 0.0348

Gnomad4 NFE AF: 0.0287

Gnomad4 OTH AF: 0.0171

Alfa AF: 0.0233 Hom.: 4

Bravo AF: 0.0200

Asia WGS AF: 0.0510 AC: 177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.7
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs41275794; hg19: chr19-52196409;