rs730880263

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5

The ENST00000265348.9(CUL7):​c.1570-3C>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

CUL7
ENST00000265348.9 splice_region, splice_polypyrimidine_tract, intron

Scores

2
Splicing: ADA: 0.9998
2

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 1.16
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 Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 6-43049665-G-T is Pathogenic according to our data. Variant chr6-43049665-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 1619.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CUL7NM_014780.5 linkuse as main transcriptc.1570-3C>A splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant ENST00000265348.9 NP_055595.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CUL7ENST00000265348.9 linkuse as main transcriptc.1570-3C>A splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 1 NM_014780.5 ENSP00000265348 P3Q14999-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

3M syndrome 1 Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMMar 01, 2009- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.41
CADD
Benign
22
DANN
Benign
0.76
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
1.0
dbscSNV1_RF
Pathogenic
0.91
SpliceAI score (max)
0.63
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.63
Position offset: 32
DS_AL_spliceai
0.53
Position offset: -3

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: rs730880263; hg19: chr6-43017403; API