rs9381231

Variant names:

• chr6-43046561-T-A
• rs9381231
• NM_014780.5:c.2438A>T

Your query was ambiguous. Multiple possible variants found:

• chr6-43046561-T-A
• chr6-43046561-T-C
• chr6-43046561-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014780.5(CUL7):​c.2438A>T​(p.Gln813Leu) 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. 14/21 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 Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CUL7 NM_014780.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.49

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14870113).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUL7	NM_014780.5	c.2438A>T	p.Gln813Leu	missense_variant	Exon 11 of 26	ENST00000265348.9	NP_055595.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUL7	ENST00000265348.9	c.2438A>T	p.Gln813Leu	missense_variant	Exon 11 of 26	1	NM_014780.5	ENSP00000265348.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 120

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.69	D;.
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.35
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.85	T;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;.
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.5	D;D
REVEL	Benign	0.18
Sift	Uncertain	0.0020	D;D
Sift4G	Benign	0.084	T;T
Polyphen		0.0020	B;.
Vest4		0.36
MutPred		0.41		Loss of disorder (P = 0.031);.;
MVP		0.70
MPC		0.21
ClinPred		0.63	D
GERP RS		1.6
Varity_R		0.23
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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

Other links and lift over

dbSNP: rs9381231; hg19: chr6-43014299;