19-51693200-T-C

Variant names:

• chr19-51693200-T-C
• rs12976445
• ENST00000602324.1:n.257A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000602324.1(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 ENST00000602324.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.575
• Publications: 64 publications found

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]

MIR125A (HGNC:31505): (microRNA 125a) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SPACA6	NM_001316972.2	c.-327T>C		upstream_gene_variant		ENST00000637797.2	NP_001303901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPACA6	ENST00000637797.2	c.-327T>C		upstream_gene_variant		1	NM_001316972.2	ENSP00000490829.1

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

African (AFR) AF: 0.663 AC: 7723 AN: 11640

American (AMR) AF: 0.353 AC: 8676 AN: 24574

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 3762 AN: 13482

East Asian (EAS) AF: 0.909 AC: 20217 AN: 22234

South Asian (SAS) AF: 0.425 AC: 23128 AN: 54432

European-Finnish (FIN) AF: 0.386 AC: 15082 AN: 39038

Middle Eastern (MID) AF: 0.313 AC: 1030 AN: 3288

European-Non Finnish (NFE) AF: 0.316 AC: 67745 AN: 214524

Other (OTH) AF: 0.375 AC: 7961 AN: 21240

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

African (AFR) AF: 0.667 AC: 27552 AN: 41338

American (AMR) AF: 0.355 AC: 5413 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 1002 AN: 3462

East Asian (EAS) AF: 0.892 AC: 4566 AN: 5120

South Asian (SAS) AF: 0.430 AC: 2068 AN: 4810

European-Finnish (FIN) AF: 0.399 AC: 4222 AN: 10574

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.320 AC: 21742 AN: 67896

Other (OTH) AF: 0.402 AC: 845 AN: 2104

Alfa AF: 0.383 Hom.: 19721

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
PhyloP100		-0.57
PromoterAI		0.025	Neutral

Splicing

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

Other links and lift over

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