20-57332287-G-A

Variant names:

• chr20-57332287-G-A
• rs79564060
• NM_012444.3:c.245+341G>A

Variant summary

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

The NM_012444.3(SPO11):​c.245+341G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0109 in 152,216 control chromosomes in the GnomAD database, including 12 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 0.011 (12 hom., cov: 33)
• Consequence: SPO11 NM_012444.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.368
• Publications: 2 publications found

Genes affected

SPO11 (HGNC:11250): (SPO11 initiator of meiotic double strand breaks) Meiotic recombination and chromosome segregation require the formation of double-strand breaks (DSBs) in paired chromosome homologs. During meiosis in yeast, a meiotic recombination protein is covalently-linked to the 5' end of DSBs and is essential for the formation of DSBs. The protein encoded by this gene is similar in sequence and conserved features to the yeast meiotic recombination protein. The encoded protein belongs to the TOP6A protein family. Several transcript variants encoding different isoforms have been found for this gene, but the full-length nature of only two of them have been described. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0109 (1665/152216) while in subpopulation NFE AF = 0.0177 (1202/68006). AF 95% confidence interval is 0.0168. There are 12 homozygotes in GnomAd4. There are 805 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012444.3. 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
	SPO11	NM_012444.3	MANE Select	c.245+341G>A		intron	N/A	NP_036576.1
	SPO11	NM_198265.2		c.132-901G>A		intron	N/A	NP_937998.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPO11	ENST00000371263.8	TSL:1 MANE Select	c.245+341G>A		intron	N/A	ENSP00000360310.3
	SPO11	ENST00000345868.8	TSL:1	c.132-901G>A		intron	N/A	ENSP00000316034.4
	SPO11	ENST00000371260.8	TSL:5	c.132-901G>A		intron	N/A	ENSP00000360307.4

Frequencies

GnomAD3 genomes AF: 0.0109 AC: 1665 AN: 152098 Hom.: 12 Cov.: 33

Gnomad AFR AF: 0.00328

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00550

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.0199

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.0177

Gnomad OTH AF: 0.00815

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0109 AC: 1665 AN: 152216 Hom.: 12 Cov.: 33 AF XY: 0.0108 AC XY: 805 AN XY: 74440

African (AFR) AF: 0.00327 AC: 136 AN: 41530

American (AMR) AF: 0.00549 AC: 84 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4822

European-Finnish (FIN) AF: 0.0199 AC: 211 AN: 10598

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 292

European-Non Finnish (NFE) AF: 0.0177 AC: 1202 AN: 68006

Other (OTH) AF: 0.00806 AC: 17 AN: 2108

Alfa AF: 0.0160 Hom.: 37

Bravo AF: 0.00951

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	2.4
DANN	Benign	0.76
PhyloP100		0.37
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs79564060; hg19: chr20-55907343;