rs10404453

chr19-51693235-G-Achr19-51693235-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NR_108100.1(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 NR_108100.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.127

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

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 14 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPACA6-AS1	NR_108100.1	n.222C>T		non_coding_transcript_exon_variant	1/2
SPACA6	NM_001316994.2	c.92-1243G>A		intron_variant
SPACA6	XM_017026300.3	c.-41-1243G>A		intron_variant
MIR125A	NR_029693.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPACA6-AS1	ENST00000602324.1	n.222C>T		non_coding_transcript_exon_variant	1/2	2
SPACA6	ENST00000646845.1	c.368-1243G>A		intron_variant
SPACA6	ENST00000710615.1	c.-41-1243G>A		intron_variant				A2
MIR125A	ENST00000385273.1			upstream_gene_variant

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

GnomAD3 exomes AF: 0.00261 AC: 475 AN: 182214 Hom.: 9 AF XY: 0.00185 AC XY: 179 AN XY: 96816

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 SAS exome AF: 0.00

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

Gnomad4 AFR exome AF: 0.0314

Gnomad4 AMR exome AF: 0.00288

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000138

Gnomad4 SAS exome AF: 0.0000656

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000151

Gnomad4 OTH exome AF: 0.00265

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

Gnomad4 AFR AF: 0.0312

Gnomad4 AMR AF: 0.00373

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.00663

Alfa AF: 0.00565 Hom.: 1

Bravo AF: 0.0107

Asia WGS AF: 0.00404 AC: 14 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	5.9
Dann	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10404453; hg19: chr19-52196488;