11-66744819-GGGCGGCGGCGGC-G

Variant summary

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

The NM_001302084.2(C11orf80):c.-115_-104del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000398 in 1,230,486 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000040 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000040 (0 hom.)
• Consequence: C11orf80 NM_001302084.2 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00

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 11-66744819-GGGCGGCGGCGGC-G is Benign according to our data. Variant chr11-66744819-GGGCGGCGGCGGC-G is described in ClinVar as [Likely_benign]. Clinvar id is 3035172.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.-115_-104del		5_prime_UTR_variant	1/15	ENST00000540737.7
C11orf80	NM_024650.3	c.92_103del	p.Ala31_Ala34del	inframe_deletion	1/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C11orf80	ENST00000540737.7	c.-115_-104del		5_prime_UTR_variant	1/15	2	NM_001302084.2	A2

Frequencies

GnomAD3 genomes AF: 0.0000405 AC: 6 AN: 148182 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000492

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000203

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000452

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000397 AC: 43 AN: 1082304 Hom.: 0 AF XY: 0.0000363 AC XY: 19 AN XY: 523460

Gnomad4 AFR exome AF: 0.0000431

Gnomad4 AMR exome AF: 0.000426

Gnomad4 ASJ exome AF: 0.0000641

Gnomad4 EAS exome AF: 0.000114

Gnomad4 SAS exome AF: 0.0000317

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000289

Gnomad4 OTH exome AF: 0.0000909

GnomAD4 genome AF: 0.0000405 AC: 6 AN: 148182 Hom.: 0 Cov.: 0 AF XY: 0.0000416 AC XY: 3 AN XY: 72136

Gnomad4 AFR AF: 0.0000492

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000203

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000452

Gnomad4 OTH AF: 0.00

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

Mar 23, 2020

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: rs567536854; hg19: chr11-66512290;