Variant 3-98516669-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001040181.2(CLDND1):c.752G>C(p.Arg251Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000316 in 1,613,966 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 (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

CLDND1
NM_001040181.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.63

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37263346).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLDND1	NM_001040181.2 linkuse as main transcript	c.752G>C	p.Arg251Pro	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.752G>C	p.Arg251Pro	missense_variant	5/5	1	NM_001040181.2	P1	Q9NY35-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000478

AC:

AN:

251174

Hom.:

AF XY:

0.0000737

AC XY:

AN XY:

135754

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000335

AC:

AN:

1461722

Hom.:

Cov.:

AF XY:

0.0000385

AC XY:

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000487

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000330

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 12, 2023

The c.821G>C (p.R274P) alteration is located in exon 6 (coding exon 6) of the CLDND1 gene. This alteration results from a G to C substitution at nucleotide position 821, causing the arginine (R) at amino acid position 274 to be replaced by a proline (P). 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

0.99

BayesDel_addAF

Uncertain

0.018

BayesDel_noAF

Uncertain

0.090

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

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

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

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

M_CAP

Benign

0.044

MetaRNN

Benign

0.37

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

MetaSVM

Benign

-0.89

MutationAssessor

Benign

2.0

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

MutationTaster

Benign

1.0

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

PrimateAI

Pathogenic

0.79

PROVEAN

Uncertain

-2.7

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

REVEL

Uncertain

0.34

Sift

Uncertain

0.0030

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

Sift4G

Uncertain

0.0070

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

Polyphen

0.99

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

Vest4

0.55

MutPred

0.59

Loss of MoRF binding (P = 0);Loss of MoRF binding (P = 0);Loss of MoRF binding (P = 0);Loss of MoRF binding (P = 0);.;Loss of MoRF binding (P = 0);.;Loss of MoRF binding (P = 0);

MVP

0.29

ClinPred

0.56

GERP RS

5.2

Varity_R

0.82

gMVP

0.78

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