Variant 19-541406-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_004359.2(CDC34):c.565G>A(p.Glu189Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000959 in 1,459,642 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

CDC34
NM_004359.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.85

Variant links:

Genes affected

CDC34 (HGNC:1734): (cell division cycle 34, ubiqiutin conjugating enzyme) The protein encoded by this gene is a member of the ubiquitin-conjugating enzyme family. Ubiquitin-conjugating enzyme catalyzes the covalent attachment of ubiquitin to other proteins. This protein is a part of the large multiprotein complex, which is required for ubiquitin-mediated degradation of cell cycle G1 regulators, and for the initiation of DNA replication. [provided by RefSeq, Jul 2008]

CDC34 links:

CDC34 (HGNC:):

CDC34 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC34	NM_004359.2 linkuse as main transcript	c.565G>A	p.Glu189Lys	missense_variant	5/5	ENST00000215574.9	NP_004350.1	P49427A0A024R1Z1
CDC34	XM_006722952.3 linkuse as main transcript	c.*21G>A		3_prime_UTR_variant	5/5		XP_006723015.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC34	ENST00000215574.9 linkuse as main transcript	c.565G>A	p.Glu189Lys	missense_variant	5/5	1	NM_004359.2	ENSP00000215574.2		P49427

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000407

AC:

AN:

245532

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133726

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000909

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000959

AC:

AN:

1459642

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726130

show subpopulations

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:

0.0000126

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000826

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 01, 2023

The c.565G>A (p.E189K) alteration is located in exon 5 (coding exon 5) of the CDC34 gene. This alteration results from a G to A substitution at nucleotide position 565, causing the glutamic acid (E) at amino acid position 189 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.92

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

T;T

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

1.0

D;D

M_CAP

Uncertain

0.14

MetaRNN

Uncertain

0.62

D;D

MetaSVM

Uncertain

-0.015

MutationAssessor

Uncertain

2.8

M;.

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-3.5

D;.

REVEL

Uncertain

0.49

Sift

Uncertain

0.0070

D;.

Sift4G

Uncertain

0.032

D;D

Polyphen

1.0

D;.

Vest4

0.75

MutPred

0.47

Gain of methylation at E189 (P = 0.0118);.;

MVP

0.70

MPC

0.13

ClinPred

0.96

GERP RS

3.9

Varity_R

0.55

gMVP

0.79

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over