11-66756337-C-CTT

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The ENST00000525449.6(C11orf80):c.-149-7_-149-6dup variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000167 in 938,592 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: C11orf80 ENST00000525449.6 splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.538

Genes affected

C11orf80 (HGNC:26197): (TOP6B like initiator of meiotic double strand breaks) Predicted to be involved in meiotic DNA double-strand break formation and reciprocal meiotic recombination. Predicted to be located in chromosome. Implicated in gestational trophoblastic neoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 11-66756337-C-CTT is Benign according to our data. Variant chr11-66756337-C-CTT is described in ClinVar as [Likely_benign]. Clinvar id is 3038989.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C11orf80	NM_001302084.2	c.-29-2697_-29-2696dup		intron_variant		ENST00000540737.7
C11orf80	NM_024650.3	c.317-7_317-6dup		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C11orf80	ENST00000540737.7	c.-29-2697_-29-2696dup		intron_variant		2	NM_001302084.2	A2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00142 AC: 36 AN: 25382 Hom.: 0 AF XY: 0.00129 AC XY: 18 AN XY: 13902

Gnomad AFR exome AF: 0.00177

Gnomad AMR exome AF: 0.000815

Gnomad ASJ exome AF: 0.00109

Gnomad EAS exome AF: 0.00118

Gnomad SAS exome AF: 0.00355

Gnomad FIN exome AF: 0.000735

Gnomad NFE exome AF: 0.00103

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.000167 AC: 157 AN: 938592 Hom.: 0 Cov.: 24 AF XY: 0.000211 AC XY: 96 AN XY: 454066

Gnomad4 AFR exome AF: 0.000219

Gnomad4 AMR exome AF: 0.000414

Gnomad4 ASJ exome AF: 0.000533

Gnomad4 EAS exome AF: 0.00106

Gnomad4 SAS exome AF: 0.000744

Gnomad4 FIN exome AF: 0.000216

Gnomad4 NFE exome AF: 0.000107

Gnomad4 OTH exome AF: 0.000209

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

TOP6BL-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 20, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs538618909; hg19: chr11-66523808;