19-51693200-T-C

Position:

• chr19-51693200-T-C

Variant summary

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

The NR_108100.1(SPACA6-AS1):​n.257A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 556,212 control chromosomes in the GnomAD database, including 52,308 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 0.45 (17371 hom., cov: 30)
  • Exomes 𝑓: 0.38 (34937 hom.)
• Consequence: SPACA6-AS1 NR_108100.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.575

Genes affected

SPACA6-AS1 (HGNC:49383): (SPACA6 antisense RNA 1)

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPACA6-AS1	NR_108100.1	n.257A>G		non_coding_transcript_exon_variant	1/2
SPACA6	NM_001316994.2	c.92-1278T>C		intron_variant			NP_001303923.1
SPACA6	XM_017026300.3	c.-41-1278T>C		intron_variant			XP_016881789.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPACA6-AS1	ENST00000602324.1	n.257A>G		non_coding_transcript_exon_variant	1/2	2
SPACA6	ENST00000646845.1	c.368-1278T>C		intron_variant				ENSP00000496692
SPACA6	ENST00000710615.1	c.-41-1278T>C		intron_variant				ENSP00000518379	A2

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67675 AN: 151642 Hom.: 17333 Cov.: 30

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.892

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.400

GnomAD4 exome AF: 0.384 AC: 155324 AN: 404452 Hom.: 34937 Cov.: 0 AF XY: 0.383 AC XY: 83000 AN XY: 216458

Gnomad4 AFR exome AF: 0.663

Gnomad4 AMR exome AF: 0.353

Gnomad4 ASJ exome AF: 0.279

Gnomad4 EAS exome AF: 0.909

Gnomad4 SAS exome AF: 0.425

Gnomad4 FIN exome AF: 0.386

Gnomad4 NFE exome AF: 0.316

Gnomad4 OTH exome AF: 0.375

GnomAD4 genome AF: 0.447 AC: 67762 AN: 151760 Hom.: 17371 Cov.: 30 AF XY: 0.450 AC XY: 33348 AN XY: 74158

Gnomad4 AFR AF: 0.667

Gnomad4 AMR AF: 0.355

Gnomad4 ASJ AF: 0.289

Gnomad4 EAS AF: 0.892

Gnomad4 SAS AF: 0.430

Gnomad4 FIN AF: 0.399

Gnomad4 NFE AF: 0.320

Gnomad4 OTH AF: 0.402

Alfa AF: 0.372 Hom.: 2450

Bravo AF: 0.459

Asia WGS AF: 0.643 AC: 2235 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.52

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12976445; hg19: chr19-52196453; COSMIC: COSV59035606;