NM_014780.5:c.339C>T

Variant names:

• chr6-43052450-G-A
• rs4711738
• NM_014780.5:c.339C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_014780.5(CUL7):​c.339C>T​(p.Asp113Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,613,918 control chromosomes in the GnomAD database, including 19,808 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (5940 hom., cov: 32)
  • Exomes 𝑓: 0.12 (13868 hom.)
• Consequence: CUL7 NM_014780.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.04
• Publications: 17 publications found

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]

ENSG00000288564 (HGNC:):

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

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 6-43052450-G-A is Benign according to our data. Variant chr6-43052450-G-A is described in ClinVar as Benign. ClinVar VariationId is 260438.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.04 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUL7	NM_014780.5	MANE Select	c.339C>T	p.Asp113Asp	synonymous	Exon 2 of 26	NP_055595.2
	CUL7	NM_001168370.2		c.339C>T	p.Asp113Asp	synonymous	Exon 2 of 26	NP_001161842.2
	CUL7	NM_001374872.1		c.339C>T	p.Asp113Asp	synonymous	Exon 2 of 26	NP_001361801.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUL7	ENST00000265348.9	TSL:1 MANE Select	c.339C>T	p.Asp113Asp	synonymous	Exon 2 of 26	ENSP00000265348.4
	ENSG00000288564	ENST00000673761.1		n.*263C>T		non_coding_transcript_exon	Exon 7 of 9	ENSP00000501018.1
	ENSG00000288564	ENST00000673761.1		n.*263C>T		3_prime_UTR	Exon 7 of 9	ENSP00000501018.1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33616 AN: 152084 Hom.: 5919 Cov.: 32

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.0978

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.0886

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0959

Gnomad OTH AF: 0.217

GnomAD2 exomes AF: 0.158 AC: 39636 AN: 251342 AF XY: 0.149

Gnomad AFR exome AF: 0.500

Gnomad AMR exome AF: 0.203

Gnomad ASJ exome AF: 0.0951

Gnomad EAS exome AF: 0.247

Gnomad FIN exome AF: 0.0869

Gnomad NFE exome AF: 0.0952

Gnomad OTH exome AF: 0.138

GnomAD4 exome AF: 0.117 AC: 171549 AN: 1461716 Hom.: 13868 Cov.: 35 AF XY: 0.117 AC XY: 85263 AN XY: 727122

African (AFR) AF: 0.499 AC: 16704 AN: 33476

American (AMR) AF: 0.204 AC: 9143 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0968 AC: 2529 AN: 26136

East Asian (EAS) AF: 0.240 AC: 9519 AN: 39698

South Asian (SAS) AF: 0.171 AC: 14708 AN: 86258

European-Finnish (FIN) AF: 0.0892 AC: 4763 AN: 53386

Middle Eastern (MID) AF: 0.142 AC: 819 AN: 5768

European-Non Finnish (NFE) AF: 0.0940 AC: 104492 AN: 1111886

Other (OTH) AF: 0.147 AC: 8872 AN: 60388

GnomAD4 genome AF: 0.221 AC: 33682 AN: 152202 Hom.: 5940 Cov.: 32 AF XY: 0.220 AC XY: 16365 AN XY: 74422

African (AFR) AF: 0.485 AC: 20139 AN: 41500

American (AMR) AF: 0.195 AC: 2982 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0978 AC: 339 AN: 3468

East Asian (EAS) AF: 0.240 AC: 1242 AN: 5176

South Asian (SAS) AF: 0.202 AC: 976 AN: 4824

European-Finnish (FIN) AF: 0.0886 AC: 941 AN: 10618

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.0960 AC: 6526 AN: 68012

Other (OTH) AF: 0.222 AC: 469 AN: 2114

Alfa AF: 0.143 Hom.: 4780

Bravo AF: 0.243

Asia WGS AF: 0.263 AC: 914 AN: 3478

EpiCase AF: 0.0948

EpiControl AF: 0.0952

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	3M syndrome 1 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.89
DANN	Benign	0.75
PhyloP100		-2.0
PromoterAI		-0.034	Neutral
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4711738; hg19: chr6-43020188; COSMIC: COSV54813228; COSMIC: COSV54813228;