19-51693235-G-A

Variant names:

• chr19-51693235-G-A
• rs10404453
• ENST00000602324.1:n.222C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000602324.1(SPACA6-AS1):​n.222C>T 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 0.00323 in 647,306 control chromosomes in the GnomAD database, including 25 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 0.0091 (16 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (9 hom.)
• Consequence: SPACA6-AS1 ENST00000602324.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.127
• Publications: 10 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=-0.88).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00912 (1387/152040) while in subpopulation AFR AF = 0.0312 (1296/41474). AF 95% confidence interval is 0.0298. There are 16 homozygotes in GnomAd4. There are 639 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 16 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000602324.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPACA6-AS1	NR_108100.1		n.222C>T		non_coding_transcript_exon	Exon 1 of 2
	SPACA6	NM_001316994.2		c.92-1243G>A		intron	N/A	NP_001303923.1
	SPACA6	NM_001316972.2	MANE Select	c.-292G>A		upstream_gene	N/A	NP_001303901.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPACA6-AS1	ENST00000602324.1	TSL:2	n.222C>T		non_coding_transcript_exon	Exon 1 of 2
	SPACA6	ENST00000710615.1		c.-41-1243G>A		intron	N/A	ENSP00000518379.1
	SPACA6	ENST00000646845.1		c.368-1243G>A		intron	N/A	ENSP00000496692.1

Frequencies

GnomAD3 genomes AF: 0.00906 AC: 1376 AN: 151920 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.0311

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00380

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.00670

GnomAD2 exomes AF: 0.00261 AC: 475 AN: 182214 AF XY: 0.00185

Gnomad AFR exome AF: 0.0329

Gnomad AMR exome AF: 0.00267

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000140

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000250

Gnomad OTH exome AF: 0.00125

GnomAD4 exome AF: 0.00142 AC: 703 AN: 495266 Hom.: 9 Cov.: 0 AF XY: 0.00114 AC XY: 303 AN XY: 265192

African (AFR) AF: 0.0314 AC: 474 AN: 15098

American (AMR) AF: 0.00288 AC: 98 AN: 34016

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17530

East Asian (EAS) AF: 0.000138 AC: 4 AN: 28958

South Asian (SAS) AF: 0.0000656 AC: 4 AN: 60968

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44946

Middle Eastern (MID) AF: 0.00380 AC: 14 AN: 3684

European-Non Finnish (NFE) AF: 0.000151 AC: 40 AN: 264070

Other (OTH) AF: 0.00265 AC: 69 AN: 25996

GnomAD4 genome AF: 0.00912 AC: 1387 AN: 152040 Hom.: 16 Cov.: 32 AF XY: 0.00860 AC XY: 639 AN XY: 74310

African (AFR) AF: 0.0312 AC: 1296 AN: 41474

American (AMR) AF: 0.00373 AC: 57 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 67972

Other (OTH) AF: 0.00663 AC: 14 AN: 2112

Alfa AF: 0.00457 Hom.: 3

Bravo AF: 0.0107

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.9
DANN	Benign	0.63
PhyloP100		0.13
PromoterAI		0.035	Neutral

Splicing

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

Other links and lift over

dbSNP: rs10404453; hg19: chr19-52196488;