Variant chr3-98521169-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.256A>G(p.Lys86Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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: 6.8e-7 ( 0 hom. )

Consequence

CLDND1
NM_001040181.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.334

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08048195).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLDND1	NM_001040181.2 linkuse as main transcript	c.256A>G	p.Lys86Glu	missense_variant	2/5	ENST00000341181.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLDND1	ENST00000341181.11 linkuse as main transcript	c.256A>G	p.Lys86Glu	missense_variant	2/5	1	NM_001040181.2	P1	Q9NY35-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251112

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135786

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461634

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727070

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

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 07, 2022

The c.325A>G (p.K109E) alteration is located in exon 3 (coding exon 3) of the CLDND1 gene. This alteration results from a A to G substitution at nucleotide position 325, causing the lysine (K) at amino acid position 109 to be replaced by a glutamic acid (E). 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

0.074

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.018

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

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.79

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

M_CAP

Benign

0.011

MetaRNN

Benign

0.080

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

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

.;N;N;.;N;N;.;N;N;.;.;.;.;.;.;.;.;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N;N;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.24

N;N;N;N;N;N;.;N;N;N;N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.074

Sift

Benign

0.44

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

Sift4G

Benign

0.70

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

Polyphen

0.0

.;B;B;.;B;B;.;B;B;.;B;.;.;.;.;.;.;.;.;.

Vest4

0.13

MutPred

0.45

Loss of methylation at K86 (P = 8e-04);Loss of methylation at K86 (P = 8e-04);Loss of methylation at K86 (P = 8e-04);.;Loss of methylation at K86 (P = 8e-04);Loss of methylation at K86 (P = 8e-04);.;Loss of methylation at K86 (P = 8e-04);Loss of methylation at K86 (P = 8e-04);.;Loss of methylation at K86 (P = 8e-04);Loss of methylation at K86 (P = 8e-04);Loss of methylation at K86 (P = 8e-04);Loss of methylation at K86 (P = 8e-04);Loss of methylation at K86 (P = 8e-04);Loss of methylation at K86 (P = 8e-04);Loss of methylation at K86 (P = 8e-04);.;Loss of methylation at K86 (P = 8e-04);Loss of methylation at K86 (P = 8e-04);

MVP

0.20

ClinPred

0.029

GERP RS

1.3

Varity_R

0.12

gMVP

0.56

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