Variant 3-98516819-T-C 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_001040181.2(CLDND1):c.602A>G(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 (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CLDND1
NM_001040181.2 missense

Scores

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]

CLDND1 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=0.09018928).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLDND1	NM_001040181.2 linkuse as main transcript	c.602A>G	p.Lys201Arg	missense_variant	5/5	ENST00000341181.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLDND1	ENST00000341181.11 linkuse as main transcript	c.602A>G	p.Lys201Arg	missense_variant	5/5	1	NM_001040181.2	P1	Q9NY35-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00

AC XY:

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.:

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 26, 2023

The 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

BayesDel_noAF

Benign

-0.40

CADD

Benign

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

LIST_S2

Benign

0.83

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

M_CAP

Benign

0.015

MetaRNN

Benign

0.090

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.91

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

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over