dbSNP rs8112073: SPACA6:c.92-1965G>A (chr19-51692513-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001316994.2(SPACA6):c.92-1965G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00383 in 434,878 control chromosomes in the GnomAD database, including 18 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 ( 15 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 3 hom. )

Consequence

SPACA6
NM_001316994.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.57

Publications

2 publications found

Variant links:

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 links:

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

SPACA6-AS1 links:

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]

MIR99B 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=-0.81).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00911 (1385/152064) while in subpopulation AFR AF = 0.0312 (1295/41484). AF 95% confidence interval is 0.0298. There are 15 homozygotes in GnomAd4. There are 637 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 15 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
SPACA6	NM_001316994.2 link	c.92-1965G>A	intron_variant	Intron 1 of 8	NP_001303923.1
SPACA6-AS1	NR_108100.1 link	n.823+121C>T	intron_variant	Intron 1 of 1
SPACA6	XM_017026300.3 link	c.-41-1965G>A	intron_variant	Intron 1 of 8	XP_016881789.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
SPACA6	ENST00000710615.1 link	c.-41-1965G>A	intron_variant	Intron 1 of 8		ENSP00000518379.1
SPACA6	ENST00000646845.1 link	c.368-1965G>A	intron_variant	Intron 1 of 1		ENSP00000496692.1	A0A2R8Y8C0
SPACA6-AS1	ENST00000602324.1 link	n.823+121C>T	intron_variant	Intron 1 of 1	2
MIR99B	ENST00000384819.1 link	n.-99G>A	upstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.00904

AC:

1374

AN:

151946

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0310

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:

0.00316

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00671

GnomAD4 exome

AF:

0.000997

AC:

282

AN:

282814

Hom.:

AF XY:

0.000837

AC XY:

136

AN XY:

162536

show subpopulations

African (AFR)

AF:

0.0305

AC:

189

AN:

6200

American (AMR)

AF:

0.00260

AC:

AN:

15016

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8360

East Asian (EAS)

AF:

0.00

AC:

AN:

9764

South Asian (SAS)

AF:

0.0000742

AC:

AN:

53938

European-Finnish (FIN)

AF:

0.00

AC:

AN:

24252

Middle Eastern (MID)

AF:

0.00309

AC:

AN:

972

European-Non Finnish (NFE)

AF:

0.000125

AC:

AN:

151808

Other (OTH)

AF:

0.00224

AC:

AN:

12504

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.00911

AC:

1385

AN:

152064

Hom.:

Cov.:

AF XY:

0.00857

AC XY:

637

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.0312

AC:

1295

AN:

41484

American (AMR)

AF:

0.00373

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000265

AC:

AN:

67938

Other (OTH)

AF:

0.00664

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

142

212

283

354

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.000374

Hom.:

Bravo

AF:

0.0107

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.9

(source)

DANN

Benign

0.43

PhyloP100

1.6

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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