11-66756337-C-CTT

Variant names:

• chr11-66756337-C-CTT
• rs538618909
• NM_001302084.2:c.-29-2697_-29-2696dupTT

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP6

The NM_024650.4(TOP6BL):​c.170-7_170-6dupTT variant causes a splice region, 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 (no stars).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: TOP6BL NM_024650.4 splice_region, intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.538

Genes affected

TOP6BL (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 1 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 no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOP6BL	NM_001302084.2	c.-29-2697_-29-2696dupTT		intron_variant	Intron 1 of 14	ENST00000540737.7	NP_001289013.1
TOP6BL	NM_024650.4	c.170-7_170-6dupTT		splice_region_variant, intron_variant	Intron 2 of 16		NP_078926.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C11orf80	ENST00000540737.7	c.-29-2706_-29-2705insTT		intron_variant	Intron 1 of 14	2	NM_001302084.2	ENSP00000444319.1
C11orf80	ENST00000525449.6	c.-149-16_-149-15insTT		intron_variant	Intron 1 of 14	1		ENSP00000434648.2

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: no assertion criteria provided

Submissions by phenotype

TOP6BL-related disorder Benign:1

Sep 20, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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;