20-57330052-G-A

Variant names:

• chr20-57330052-G-A
• rs28368064
• NM_012444.3:c.131+54G>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.131+54G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0217 in 1,506,254 control chromosomes in the GnomAD database, including 438 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 0.015 (18 hom., cov: 32)
  • Exomes 𝑓: 0.022 (420 hom.)
• Consequence: SPO11 NM_012444.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.06
• Publications: 4 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=-0.87).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0154 (2346/152348) while in subpopulation NFE AF = 0.0237 (1612/68028). AF 95% confidence interval is 0.0227. There are 18 homozygotes in GnomAd4. There are 1100 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 18 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.131+54G>A		intron	N/A	NP_036576.1
	SPO11	NM_198265.2		c.131+54G>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.131+54G>A		intron	N/A	ENSP00000360310.3
	SPO11	ENST00000345868.8	TSL:1	c.131+54G>A		intron	N/A	ENSP00000316034.4
	SPO11	ENST00000371260.8	TSL:5	c.131+54G>A		intron	N/A	ENSP00000360307.4

Frequencies

GnomAD3 genomes AF: 0.0154 AC: 2345 AN: 152230 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.00456

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.00962

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0178

Gnomad FIN AF: 0.0200

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0237

Gnomad OTH AF: 0.0201

GnomAD4 exome AF: 0.0224 AC: 30361 AN: 1353906 Hom.: 420 AF XY: 0.0225 AC XY: 14960 AN XY: 664010

African (AFR) AF: 0.00374 AC: 115 AN: 30728

American (AMR) AF: 0.00981 AC: 322 AN: 32834

Ashkenazi Jewish (ASJ) AF: 0.0171 AC: 400 AN: 23402

East Asian (EAS) AF: 0.0000847 AC: 3 AN: 35416

South Asian (SAS) AF: 0.0238 AC: 1818 AN: 76256

European-Finnish (FIN) AF: 0.0223 AC: 777 AN: 34844

Middle Eastern (MID) AF: 0.0215 AC: 96 AN: 4456

European-Non Finnish (NFE) AF: 0.0243 AC: 25741 AN: 1059802

Other (OTH) AF: 0.0194 AC: 1089 AN: 56168

GnomAD4 genome AF: 0.0154 AC: 2346 AN: 152348 Hom.: 18 Cov.: 32 AF XY: 0.0148 AC XY: 1100 AN XY: 74500

African (AFR) AF: 0.00455 AC: 189 AN: 41584

American (AMR) AF: 0.00960 AC: 147 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0130 AC: 45 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.0178 AC: 86 AN: 4826

European-Finnish (FIN) AF: 0.0200 AC: 212 AN: 10626

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0237 AC: 1612 AN: 68028

Other (OTH) AF: 0.0198 AC: 42 AN: 2116

Alfa AF: 0.0204 Hom.: 39

Bravo AF: 0.0139

Asia WGS AF: 0.00779 AC: 28 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.73
DANN	Benign	0.86
PhyloP100		-3.1
PromoterAI		-0.040	Neutral
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: rs28368064; hg19: chr20-55905108;