dbSNP rs759408749: CLDN10:p.Asn48Lys (chr13-95552897-C-A) – ACMG Classification: Likely_pathogenic (8 pts)

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PS1PM2PP3_Moderate

The NM_006984.5(CLDN10):c.144C>A(p.Asn48Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Pathogenic in Lovd.

Frequency

Genomes: not found (cov: 33)

Consequence

CLDN10
NM_006984.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.18

Variant links:

Genes affected

CLDN10 (HGNC:2033): (claudin 10) This gene encodes a member of the claudin family. Claudins are integral membrane proteins and components of tight junction strands. Tight junction strands serve as a physical barrier to prevent solutes and water from passing freely through the paracellular space between epithelial or endothelial cell sheets, and also play critical roles in maintaining cell polarity and signal transductions. The expression level of this gene is associated with recurrence of primary hepatocellular carcinoma. Six alternatively spliced transcript variants encoding different isoforms have been reported, but the transcript sequences of some variants are not determined.[provided by RefSeq, Jun 2010]

CLDN10 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

PS1

Transcript NM_006984.5 (CLDN10) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in Lovd

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.915

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLDN10	NM_006984.5 link	c.144C>A	p.Asn48Lys	missense_variant	Exon 1 of 5	ENST00000299339.3	NP_008915.1	P78369-1
CLDN10	XM_047430765.1 link	c.-3108C>A		5_prime_UTR_variant	Exon 1 of 6		XP_047286721.1
CLDN10	NM_182848.4 link	c.215-7235C>A		intron_variant	Intron 1 of 4		NP_878268.1	P78369-2
CLDN10	NM_001160100.2 link	c.158-7235C>A		intron_variant	Intron 1 of 4		NP_001153572.1	P78369-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLDN10	ENST00000299339.3 link	c.144C>A	p.Asn48Lys	missense_variant	Exon 1 of 5	1	NM_006984.5	ENSP00000299339.2		P78369-1
CLDN10	ENST00000376873.7 link	c.215-7235C>A		intron_variant	Intron 1 of 4	2		ENSP00000366069.2		P78369-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251288

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135858

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:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.030

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.82

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.90

M_CAP

Pathogenic

0.39

MetaRNN

Pathogenic

0.91

MetaSVM

Uncertain

0.77

MutationAssessor

Pathogenic

3.1

PrimateAI

Uncertain

0.77

PROVEAN

Pathogenic

-5.4

REVEL

Pathogenic

0.83

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.016

Polyphen

1.0

Vest4

0.69

MutPred

0.78

Gain of methylation at N48 (P = 0.0122);

MVP

0.97

MPC

1.2

ClinPred

0.99

GERP RS

4.0

Varity_R

0.73

gMVP

0.96

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over