rs73733791

Variant names:

• chr6-43050999-C-G
• NM_014780.5:c.1202G>C

Your query was ambiguous. Multiple possible variants found:

• chr6-43050999-C-G
• chr6-43050999-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_014780.5(CUL7):​c.1202G>C​(p.Arg401Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CUL7 NM_014780.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17

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]

ENSG00000288564 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.788

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUL7	NM_014780.5	c.1202G>C	p.Arg401Pro	missense_variant	Exon 4 of 26	ENST00000265348.9	NP_055595.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUL7	ENST00000265348.9	c.1202G>C	p.Arg401Pro	missense_variant	Exon 4 of 26	1	NM_014780.5	ENSP00000265348.4
ENSG00000288564	ENST00000673761.1	n.*1236G>C		downstream_gene_variant				ENSP00000501018.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461872 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727236

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.76	D;.
Eigen	Benign	0.17
Eigen_PC	Benign	0.050
FATHMM_MKL	Benign	0.65	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.79	D;D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-3.0	D;D
REVEL	Uncertain	0.55
Sift	Uncertain	0.0080	D;D
Sift4G	Uncertain	0.013	D;D
Polyphen		0.97	D;.
Vest4		0.69
MutPred		0.24		Loss of sheet (P = 0.0357);.;
MVP		0.86
MPC		0.89
ClinPred		0.97	D
GERP RS		1.5
Varity_R		0.70
gMVP		0.83

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-43018737;