rs28368064

chr20-57330052-G-Achr20-57330052-G-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPO11	NM_012444.3	c.131+54G>A		intron_variant		ENST00000371263.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPO11	ENST00000371263.8	c.131+54G>A		intron_variant		1	NM_012444.3	P1
SPO11	ENST00000345868.8	c.131+54G>A		intron_variant		1
SPO11	ENST00000371260.8	c.131+54G>A		intron_variant		5
SPO11	ENST00000418127.5	c.65+54G>A		intron_variant		3

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

Gnomad4 AFR exome AF: 0.00374

Gnomad4 AMR exome AF: 0.00981

Gnomad4 ASJ exome AF: 0.0171

Gnomad4 EAS exome AF: 0.0000847

Gnomad4 SAS exome AF: 0.0238

Gnomad4 FIN exome AF: 0.0223

Gnomad4 NFE exome AF: 0.0243

Gnomad4 OTH exome AF: 0.0194

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

Gnomad4 AFR AF: 0.00455

Gnomad4 AMR AF: 0.00960

Gnomad4 ASJ AF: 0.0130

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0178

Gnomad4 FIN AF: 0.0200

Gnomad4 NFE AF: 0.0237

Gnomad4 OTH AF: 0.0198

Alfa AF: 0.0204 Hom.: 34

Bravo AF: 0.0139

Asia WGS AF: 0.00779 AC: 28 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.73
Dann	Benign	0.86

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

Publications

LitVar

Other links and lift over

dbSNP: rs28368064; hg19: chr20-55905108;