11-66842871-CAA-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

The NM_001302084.2(C11orf80):c.1273_1274del(p.Lys425GlufsTer41) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000352 in 1,419,834 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: C11orf80 NM_001302084.2 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 1.79

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]

RCE1 (HGNC:13721): (Ras converting CAAX endopeptidase 1) This gene encodes an integral membrane protein which is classified as a member of the metalloproteinase family. This enzyme is thought to function in the maintenance and processing of CAAX-type prenylated proteins. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 11-66842871-CAA-C is Pathogenic according to our data. Variant chr11-66842871-CAA-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2571602.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.1273_1274del	p.Lys425GlufsTer41	frameshift_variant	14/15	ENST00000540737.7
C11orf80	NM_024650.3	c.1771_1772del	p.Lys591GlufsTer41	frameshift_variant	16/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C11orf80	ENST00000540737.7	c.1273_1274del	p.Lys425GlufsTer41	frameshift_variant	14/15	2	NM_001302084.2	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000352 AC: 5 AN: 1419834 Hom.: 0 AF XY: 0.00000427 AC XY: 3 AN XY: 702490

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000275

Gnomad4 OTH exome AF: 0.0000340

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hydatidiform mole, recurrent, 4 Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Medical Genetics Laboratory, Tarbiat Modares University

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-66610342;