dbSNP rs41275794: SPACA6-AS1:n.301C>T (chr19-51693156-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000602324.1(SPACA6-AS1):n.301C>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 0.0251 in 445,190 control chromosomes in the GnomAD database, including 267 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 0.022 ( 72 hom., cov: 32)

Exomes 𝑓: 0.027 ( 195 hom. )

Consequence

SPACA6-AS1
ENST00000602324.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.00

Publications

19 publications found

Variant links:

Genes affected

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

SPACA6-AS1 links:

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 links:

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]

MIR125A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPACA6	NM_001316972.2 link	c.-371G>A		upstream_gene_variant		ENST00000637797.2	NP_001303901.1	W5XKT8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPACA6	ENST00000637797.2 link	c.-371G>A		upstream_gene_variant		1	NM_001316972.2	ENSP00000490829.1		W5XKT8-1

Frequencies

GnomAD3 genomes

AF:

0.0223

AC:

3381

AN:

151902

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00561

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.0120

Gnomad ASJ

AF:

0.0135

Gnomad EAS

AF:

0.0990

Gnomad SAS

AF:

0.00787

Gnomad FIN

AF:

0.0348

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0287

Gnomad OTH

AF:

0.0129

GnomAD4 exome

AF:

0.0265

AC:

7777

AN:

293170

Hom.:

195

Cov.:

AF XY:

0.0249

AC XY:

3919

AN XY:

157076

show subpopulations

African (AFR)

AF:

0.00432

AC:

AN:

8110

American (AMR)

AF:

0.00577

AC:

AN:

16806

Ashkenazi Jewish (ASJ)

AF:

0.0124

AC:

100

AN:

8084

East Asian (EAS)

AF:

0.103

AC:

1458

AN:

14134

South Asian (SAS)

AF:

0.00954

AC:

428

AN:

44866

European-Finnish (FIN)

AF:

0.0315

AC:

934

AN:

29624

Middle Eastern (MID)

AF:

0.00401

AC:

AN:

2742

European-Non Finnish (NFE)

AF:

0.0285

AC:

4378

AN:

153874

Other (OTH)

AF:

0.0225

AC:

336

AN:

14930

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

356

712

1068

1424

1780

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

168

210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0223

AC:

3389

AN:

152020

Hom.:

Cov.:

AF XY:

0.0226

AC XY:

1677

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.00560

AC:

232

AN:

41444

American (AMR)

AF:

0.0120

AC:

183

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.0135

AC:

AN:

3472

East Asian (EAS)

AF:

0.0986

AC:

509

AN:

5162

South Asian (SAS)

AF:

0.00808

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0348

AC:

368

AN:

10572

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0287

AC:

1954

AN:

67968

Other (OTH)

AF:

0.0171

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

166

332

498

664

830

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0154

Hom.:

Bravo

AF:

0.0200

Asia WGS

AF:

0.0510

AC:

177

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

1.7

(source)

DANN

Benign

0.69

PhyloP100

-1.0

PromoterAI

-0.021

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over