Variant chr11-66842871-CAA-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate

The ENST00000525449.6(C11orf80):c.1195_1196delAA(p.Lys399fs) 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
ENST00000525449.6 frameshift

Scores

Not classified

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 1.79

Variant links:

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]

TOP6BL links:

RCE1 (HGNC:):

RCE1 links:

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ACMG classification

Classification made for transcript

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	Protein	UniProt
TOP6BL	NM_001302084.2 linkuse as main transcript	c.1273_1274delAA	p.Lys425fs	frameshift_variant	14/15	ENST00000540737.7	NP_001289013.1	Q8N6T0B4DXL1
TOP6BL	NM_024650.3 linkuse as main transcript	c.1771_1772delAA	p.Lys591fs	frameshift_variant	16/17		NP_078926.4	Q8N6T0-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C11orf80	ENST00000540737.7 linkuse as main transcript	c.1273_1274delAA	p.Lys425fs	frameshift_variant	14/15	2	NM_001302084.2	ENSP00000444319.1		B4DXL1
C11orf80	ENST00000525449.6 linkuse as main transcript	c.1195_1196delAA	p.Lys399fs	frameshift_variant	14/15	1		ENSP00000434648.2		A0A140TA08

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000352

AC:

AN:

1419834

Hom.:

AF XY:

0.00000427

AC XY:

AN XY:

702490

show subpopulations

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.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Hydatidiform mole, recurrent, 4

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Medical Genetics Laboratory, Tarbiat Modares University

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over