rs786205651

Variant summary

Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong

The ENST00000265348.9(CUL7):​c.263del​(p.Val88AlafsTer27) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Consequence

CUL7
ENST00000265348.9 frameshift

Scores

Not classified

Clinical Significance

Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:2

Conservation

PhyloP100: 3.26
Variant links:
Genes affected
CUL7 (HGNC:21024): (cullin 7) The protein encoded by this gene is a component of an E3 ubiquitin-protein ligase complex. The encoded protein interacts with TP53, CUL9, and FBXW8 proteins. Defects in this gene are a cause of 3M syndrome type 1 (3M1). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2009]
KLC4 (HGNC:21624): (kinesin light chain 4) Predicted to be located in cytoplasm and microtubule. Predicted to be part of kinesin complex. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 18 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 6-43052525-GA-G is Pathogenic according to our data. Variant chr6-43052525-GA-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 191331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-43052525-GA-G is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CUL7NM_014780.5 linkuse as main transcriptc.263del p.Val88AlafsTer27 frameshift_variant 2/26 ENST00000265348.9 NP_055595.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CUL7ENST00000265348.9 linkuse as main transcriptc.263del p.Val88AlafsTer27 frameshift_variant 2/261 NM_014780.5 ENSP00000265348 P3Q14999-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

3M syndrome 1 Pathogenic:1
Pathogenic, criteria provided, single submitterresearchAl Jalila Children’s Genomics Center, Al Jalila Childrens Speciality HospitalOct 04, 2024PVS1,PM2,PP1 -
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitterresearchCenter for Genomic Medicine, King Faisal Specialist Hospital and Research Center-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs786205651; hg19: chr6-43020263; API