Variant 3-133584055-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_017548.5(CDV3):c.371G>T(p.Trp124Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,459,248 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

CDV3
NM_017548.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.28

Variant links:

Genes affected

CDV3 (HGNC:26928): (CDV3 homolog) Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CDV3 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
CDV3	NM_017548.5 linkuse as main transcript	c.371G>T	p.Trp124Leu	missense_variant	3/5	ENST00000264993.8	NP_060018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDV3	ENST00000264993.8 linkuse as main transcript	c.371G>T	p.Trp124Leu	missense_variant	3/5	1	NM_017548.5	ENSP00000264993	P3	Q9UKY7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251138

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135744

show subpopulations

Gnomad AFR exome

AF:

0.0000616

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:

0.0000462

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1459248

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

726162

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:

0.0000162

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.00000756

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

Nov 22, 2022

The c.371G>T (p.W124L) alteration is located in exon 3 (coding exon 3) of the CDV3 gene. This alteration results from a G to T substitution at nucleotide position 371, causing the tryptophan (W) at amino acid position 124 to be replaced by a leucine (L). 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

Uncertain

0.52

BayesDel_addAF

Benign

-0.028

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.24

T;.;T;.;T;.;.;.

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.94

D;D;D;D;D;D;D;D

M_CAP

Benign

0.0086

MetaRNN

Uncertain

0.69

D;D;D;D;D;D;D;D

MetaSVM

Uncertain

-0.26

MutationAssessor

Uncertain

2.0

M;M;.;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.71

PROVEAN

Pathogenic

-5.8

D;D;D;D;D;D;D;D

REVEL

Benign

0.28

Sift

Benign

0.041

D;T;D;D;D;D;D;D

Sift4G

Benign

0.65

T;T;D;D;D;D;D;D

Polyphen

0.99

D;D;.;D;.;.;.;.

Vest4

0.54

MutPred

0.31

Gain of loop (P = 0.4248);Gain of loop (P = 0.4248);.;.;.;.;.;.;

MVP

0.56

MPC

0.82

ClinPred

0.91

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.59

gMVP

0.070

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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