3-98516819-T-C

Variant summary

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

The NM_001040181.2(CLDND1):ā€‹c.602A>Gā€‹(p.Lys201Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

CLDND1
NM_001040181.2 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.36
Variant links:
Genes affected
CLDND1 (HGNC:1322): (claudin domain containing 1) Located in cell surface. [provided by Alliance of Genome Resources, Apr 2022]

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=0.09018928).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CLDND1NM_001040181.2 linkuse as main transcriptc.602A>G p.Lys201Arg missense_variant 5/5 ENST00000341181.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CLDND1ENST00000341181.11 linkuse as main transcriptc.602A>G p.Lys201Arg missense_variant 5/51 NM_001040181.2 P1Q9NY35-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461880
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
727238
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsApr 26, 2023The c.671A>G (p.K224R) alteration is located in exon 6 (coding exon 6) of the CLDND1 gene. This alteration results from a A to G substitution at nucleotide position 671, causing the lysine (K) at amino acid position 224 to be replaced by an arginine (R). 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
0.12
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
16
DANN
Benign
0.82
DEOGEN2
Benign
0.030
T;T;T;T;T;.;T;.;T;T;.;.;T;T;T;.
Eigen
Benign
-0.45
Eigen_PC
Benign
-0.26
FATHMM_MKL
Benign
0.69
D
LIST_S2
Benign
0.83
T;.;.;.;T;T;.;T;.;T;T;T;T;T;T;T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.090
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
1.2
L;L;L;L;.;.;L;.;L;.;.;.;.;.;.;.
MutationTaster
Benign
1.0
D;D;N;N;N;N;N;N;N;N;N
PrimateAI
Benign
0.47
T
PROVEAN
Benign
-1.2
N;N;N;N;.;N;N;N;N;N;N;N;N;N;N;N
REVEL
Benign
0.066
Sift
Benign
0.63
T;T;T;T;.;T;T;T;T;T;T;T;T;T;T;T
Sift4G
Benign
0.50
T;T;T;T;T;T;T;T;T;.;.;.;.;.;.;T
Polyphen
0.0060
B;B;B;B;.;.;B;.;B;.;B;.;.;.;.;.
Vest4
0.11
MutPred
0.34
Loss of ubiquitination at K201 (P = 0.0174);Loss of ubiquitination at K201 (P = 0.0174);Loss of ubiquitination at K201 (P = 0.0174);Loss of ubiquitination at K201 (P = 0.0174);.;.;Loss of ubiquitination at K201 (P = 0.0174);.;Loss of ubiquitination at K201 (P = 0.0174);.;Loss of ubiquitination at K201 (P = 0.0174);Loss of ubiquitination at K201 (P = 0.0174);.;Loss of ubiquitination at K201 (P = 0.0174);.;Loss of ubiquitination at K201 (P = 0.0174);
MVP
0.34
ClinPred
0.10
T
GERP RS
5.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.034
gMVP
0.15

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-98235663; API