Variant 3-133574217-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017548.5(CDV3):c.173C>T(p.Pro58Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 146,922 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 32)

Consequence

CDV3
NM_017548.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.549

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.075586736).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDV3	NM_017548.5 linkuse as main transcript	c.173C>T	p.Pro58Leu	missense_variant	1/5	ENST00000264993.8	NP_060018.1	Q9UKY7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CDV3	ENST00000264993.8 linkuse as main transcript	c.173C>T	p.Pro58Leu	missense_variant	1/5	1	NM_017548.5	ENSP00000264993.3	Q9UKY7-1
CDV3	ENST00000431519.6 linkuse as main transcript	c.173C>T	p.Pro58Leu	missense_variant	1/5	1		ENSP00000391955.2	Q9UKY7-2
CDV3	ENST00000688838.1 linkuse as main transcript	c.173C>T	p.Pro58Leu	missense_variant	1/5			ENSP00000508628.1	A0A8I5KX85
CDV3	ENST00000503932.6 linkuse as main transcript	n.136+37C>T		intron_variant		4		ENSP00000421340.2	H0Y8K3

Frequencies

GnomAD3 genomes

AF:

0.0000136

AC:

AN:

146922

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000676

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000136

AC:

AN:

146922

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

71460

show subpopulations

Gnomad4 AFR

AF:

0.0000244

Gnomad4 AMR

AF:

0.0000676

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000378

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

Apr 04, 2023

The c.173C>T (p.P58L) alteration is located in exon 1 (coding exon 1) of the CDV3 gene. This alteration results from a C to T substitution at nucleotide position 173, causing the proline (P) at amino acid position 58 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

Benign

0.13

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

T;.

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.042

LIST_S2

Benign

0.50

T;T

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.076

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.0

L;L

MutationTaster

Benign

0.85

N;N

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.046

Sift

Benign

0.44

T;T

Sift4G

Benign

0.32

T;T

Polyphen

0.42

B;B

Vest4

0.085

MutPred

0.18

Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);

MVP

0.27

MPC

2.5

ClinPred

0.56

GERP RS

2.4

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.1

Varity_R

0.046

gMVP

0.095

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

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