Genetic Variant CUL7:p.Gln813His (chr6-43046560-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014780.5(CUL7):c.2439A>C(p.Gln813His) variant causes a missense 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q813R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 31)

Failed GnomAD Quality Control

Consequence

CUL7
NM_014780.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.505

Publications

16 publications found

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]

CUL7 links:

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]

KLC4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14326525).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014780.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CUL7	NM_014780.5	MANE Select	c.2439A>C	p.Gln813His	missense	Exon 11 of 26	NP_055595.2
CUL7	NM_001168370.2		c.2535A>C	p.Gln845His	missense	Exon 11 of 26	NP_001161842.2
CUL7	NM_001374872.1		c.2535A>C	p.Gln845His	missense	Exon 11 of 26	NP_001361801.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CUL7	ENST00000265348.9	TSL:1 MANE Select	c.2439A>C	p.Gln813His	missense	Exon 11 of 26	ENSP00000265348.4
CUL7	ENST00000674100.1		c.2535A>C	p.Gln845His	missense	Exon 11 of 26	ENSP00000501292.1
CUL7	ENST00000674134.1		c.2535A>C	p.Gln845His	missense	Exon 11 of 26	ENSP00000501068.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152110

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

119

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

152110

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74312

African (AFR)

AF:

0.00

AC:

AN:

41392

American (AMR)

AF:

0.00

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2086

Alfa

AF:

0.00

Hom.:

59471

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.32

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.28

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.58

M_CAP

Benign

0.032

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.69

PhyloP100

0.51

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.9

REVEL

Benign

0.046

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.015

Polyphen

0.24

Vest4

0.25

MutPred

0.23

Gain of glycosylation at T811 (P = 0.0582)

MVP

0.73

MPC

0.46

ClinPred

0.76

GERP RS

1.2

Varity_R

0.14

gMVP

0.36

Mutation Taster

=82/18

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over