rs41275792

Variant names:

• chr19-51692914-G-C
• rs41275792
• NM_001316994.2:c.92-1564G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001316994.2(SPACA6):​c.92-1564G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000895 in 529,612 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00079 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00094 (0 hom.)
• Consequence: SPACA6 NM_001316994.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.285

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:49383): (SPACA6 antisense RNA 1)

MIRLET7E (HGNC:31482): (microRNA let-7e) 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]

MIR99B (HGNC:31651): (microRNA 99b) 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPACA6	NM_001316994.2	c.92-1564G>C		intron_variant	Intron 1 of 8		NP_001303923.1
SPACA6	XM_017026300.3	c.-41-1564G>C		intron_variant	Intron 1 of 8		XP_016881789.1
SPACA6-AS1	NR_108100.1	n.543C>G		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPACA6	ENST00000710615.1	c.-41-1564G>C		intron_variant	Intron 1 of 8			ENSP00000518379.1
SPACA6	ENST00000646845.1	c.368-1564G>C		intron_variant	Intron 1 of 1			ENSP00000496692.1
SPACA6-AS1	ENST00000602324.1	n.543C>G		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.000789 AC: 120 AN: 152106 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00109

Gnomad OTH AF: 0.000958

GnomAD3 exomes AF: 0.000831 AC: 199 AN: 239550 Hom.: 0 AF XY: 0.000944 AC XY: 123 AN XY: 130264

Gnomad AFR exome AF: 0.000263

Gnomad AMR exome AF: 0.00103

Gnomad ASJ exome AF: 0.000103

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00125

Gnomad FIN exome AF: 0.0000952

Gnomad NFE exome AF: 0.00109

Gnomad OTH exome AF: 0.000683

GnomAD4 exome AF: 0.000938 AC: 354 AN: 377506 Hom.: 0 Cov.: 0 AF XY: 0.00101 AC XY: 217 AN XY: 214630

Gnomad4 AFR exome AF: 0.000193

Gnomad4 AMR exome AF: 0.000917

Gnomad4 ASJ exome AF: 0.0000866

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00125

Gnomad4 FIN exome AF: 0.000219

Gnomad4 NFE exome AF: 0.00107

Gnomad4 OTH exome AF: 0.000979

GnomAD4 genome AF: 0.000789 AC: 120 AN: 152106 Hom.: 0 Cov.: 32 AF XY: 0.000902 AC XY: 67 AN XY: 74314

Gnomad4 AFR AF: 0.000290

Gnomad4 AMR AF: 0.00190

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00109

Gnomad4 OTH AF: 0.000958

Alfa AF: 0.000861 Hom.: 0

Bravo AF: 0.000835

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.1
DANN	Benign	0.90

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs41275792; hg19: chr19-52196167;