chr20-57332287-G-A

Position:

• chr20-57332287-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.76).
• 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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPO11	NM_012444.3	c.245+341G>A		intron_variant		ENST00000371263.8	NP_036576.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPO11	ENST00000371263.8	c.245+341G>A		intron_variant		1	NM_012444.3	ENSP00000360310	P1
SPO11	ENST00000345868.8	c.132-901G>A		intron_variant		1		ENSP00000316034
SPO11	ENST00000371260.8	c.132-901G>A		intron_variant		5		ENSP00000360307
SPO11	ENST00000418127.5	c.179+341G>A		intron_variant		3		ENSP00000413185

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

Gnomad4 AFR AF: 0.00327

Gnomad4 AMR AF: 0.00549

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.0199

Gnomad4 NFE AF: 0.0177

Gnomad4 OTH AF: 0.00806

Alfa AF: 0.0146 Hom.: 5

Bravo AF: 0.00951

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	2.4
DANN	Benign	0.76

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: rs79564060; hg19: chr20-55907343;