Variant 16-4514105-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_013399.3(CDIP1):c.26A>G(p.Tyr9Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000158 in 1,392,284 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: 0.000016 ( 0 hom. )

Consequence

CDIP1
NM_013399.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.17

Variant links:

Genes affected

CDIP1 (HGNC:13234): (cell death inducing p53 target 1) Predicted to enable metal ion binding activity. Acts upstream of or within intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator and tumor necrosis factor-mediated signaling pathway. Located in cytoplasmic side of late endosome membrane; cytoplasmic side of lysosomal membrane; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

CDIP1 links:

Genome browser will be placed here

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	UniProt
CDIP1	NM_013399.3 linkuse as main transcript	c.26A>G	p.Tyr9Cys	missense_variant	3/6	ENST00000567695.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDIP1	ENST00000567695.6 linkuse as main transcript	c.26A>G	p.Tyr9Cys	missense_variant	3/6	1	NM_013399.3	P1	Q9H305-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000556

AC:

AN:

179738

Hom.:

AF XY:

0.00000992

AC XY:

AN XY:

100758

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:

0.0000113

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000158

AC:

AN:

1392284

Hom.:

Cov.:

AF XY:

0.0000101

AC XY:

AN XY:

691836

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:

0.0000202

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000828

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

Dec 20, 2023

The c.26A>G (p.Y9C) alteration is located in exon 3 (coding exon 1) of the CDIP1 gene. This alteration results from a A to G substitution at nucleotide position 26, causing the tyrosine (Y) at amino acid position 9 to be replaced by a cysteine (C). 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

0.84

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.11

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.053

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

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

0.99

M_CAP

Uncertain

0.23

MetaRNN

Uncertain

0.59

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

MetaSVM

Uncertain

0.66

MutationAssessor

Uncertain

2.2

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

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-2.1

N;N;N;D;D;.;.;.;.

Sift

Pathogenic

0.0

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

Sift4G

Uncertain

0.0050

D;D;D;D;D;T;.;T;.

Polyphen

1.0

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

Vest4

0.64

MutPred

0.29

Loss of phosphorylation at Y9 (P = 0.0158);Loss of phosphorylation at Y9 (P = 0.0158);Loss of phosphorylation at Y9 (P = 0.0158);Loss of phosphorylation at Y9 (P = 0.0158);Loss of phosphorylation at Y9 (P = 0.0158);Loss of phosphorylation at Y9 (P = 0.0158);Loss of phosphorylation at Y9 (P = 0.0158);Loss of phosphorylation at Y9 (P = 0.0158);Loss of phosphorylation at Y9 (P = 0.0158);

MVP

0.53

MPC

0.80

ClinPred

0.86

GERP RS

5.5

Varity_R

0.54

gMVP

0.57

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