chr15-36645230-T-G

Variant summary

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

The NM_001321759.2(CDIN1):ā€‹c.155T>Gā€‹(p.Ile52Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000451 in 1,551,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000036 ( 0 hom. )

Consequence

CDIN1
NM_001321759.2 missense

Scores

1
7
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.79
Variant links:
Genes affected
CDIN1 (HGNC:26929): (CDAN1 interacting nuclease 1) This gene encodes a protein with two predicted helix-turn-helix domains. Mutations in this gene were found in families with congenital dyserythropoietic anemia type Ib. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2014]

Genome browser will be placed here

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=0.17126691).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CDIN1NM_001321759.2 linkuse as main transcriptc.155T>G p.Ile52Ser missense_variant 3/11 ENST00000566621.6 NP_001308688.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CDIN1ENST00000566621.6 linkuse as main transcriptc.155T>G p.Ile52Ser missense_variant 3/115 NM_001321759.2 ENSP00000455397 P1Q9Y2V0-1
ENST00000565366.1 linkuse as main transcriptn.122-3270A>C intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
152082
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000127
AC:
2
AN:
157688
Hom.:
0
AF XY:
0.0000120
AC XY:
1
AN XY:
83660
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:
0.0000323
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000357
AC:
5
AN:
1399752
Hom.:
0
Cov.:
31
AF XY:
0.00000434
AC XY:
3
AN XY:
690530
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:
0.00000463
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
152082
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74280
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000624
Hom.:
0
Bravo
AF:
0.0000151

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 09, 2023This sequence change replaces isoleucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 52 of the C15orf41 protein (p.Ile52Ser). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with C15orf41-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt C15orf41 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.80
BayesDel_addAF
Benign
-0.031
T
BayesDel_noAF
Benign
-0.18
CADD
Uncertain
24
DANN
Uncertain
0.98
DEOGEN2
Benign
0.099
T;.;.;T;.;T
Eigen
Benign
-0.061
Eigen_PC
Benign
0.082
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.91
.;D;D;.;D;D
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.17
T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.0
M;.;.;M;.;M
MutationTaster
Benign
0.99
D;D;D;D;D;D
PROVEAN
Uncertain
-2.5
D;.;D;.;.;D
REVEL
Benign
0.15
Sift
Uncertain
0.0070
D;.;D;.;.;D
Sift4G
Uncertain
0.014
D;.;D;.;.;D
Polyphen
0.22
B;.;.;B;.;B
Vest4
0.78
MutPred
0.45
Loss of stability (P = 0.0162);Loss of stability (P = 0.0162);Loss of stability (P = 0.0162);Loss of stability (P = 0.0162);Loss of stability (P = 0.0162);Loss of stability (P = 0.0162);
MVP
0.28
MPC
0.23
ClinPred
0.31
T
GERP RS
4.4
Varity_R
0.33
gMVP
0.62

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.

Other links and lift over

dbSNP: rs1229501258; hg19: chr15-36937431; API