rs930701747

Variant names:

• chr13-95552755-T-C
• rs930701747
• NM_006984.5:c.2T>C

Your query was ambiguous. Multiple possible variants found:

• chr13-95552755-T-C
• chr13-95552755-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PVS1_Moderate PM2 PP5

The NM_006984.5(CLDN10):​c.2T>C​(p.Met1?) variant causes a start lost change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CLDN10 NM_006984.5 start_lost
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.66
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• HELIX syndrome

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet, Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

• PVS1: Start lost variant, next in-frame start position is after 1 pathogenic variants. Next in-frame start position is after 12 codons. Genomic position: 95552787. Lost 0.049 part of the original CDS.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 13-95552755-T-C is Pathogenic according to our data. Variant chr13-95552755-T-C is described in ClinVar as Pathogenic. ClinVar VariationId is 438638.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLDN10	NM_006984.5	c.2T>C	p.Met1?	start_lost	Exon 1 of 5	ENST00000299339.3	NP_008915.1
CLDN10	XM_047430765.1	c.-3250T>C		5_prime_UTR_variant	Exon 1 of 6		XP_047286721.1
CLDN10	NM_182848.4	c.215-7377T>C		intron_variant	Intron 1 of 4		NP_878268.1
CLDN10	NM_001160100.2	c.158-7377T>C		intron_variant	Intron 1 of 4		NP_001153572.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLDN10	ENST00000299339.3	c.2T>C	p.Met1?	start_lost	Exon 1 of 5	1	NM_006984.5	ENSP00000299339.2
CLDN10	ENST00000376873.7	c.215-7377T>C		intron_variant	Intron 1 of 4	2		ENSP00000366069.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

HELIX syndrome Pathogenic:1

Nov 20, 2018

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.47	D
BayesDel_noAF	Pathogenic	0.44
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.63	D
LIST_S2	Uncertain	0.90	D
M_CAP	Pathogenic	0.95	D
MetaRNN	Pathogenic	0.99	D
MetaSVM	Pathogenic	0.90	D
PhyloP100		3.7
PROVEAN	Benign	-0.79	N
REVEL	Pathogenic	0.71
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.74
MutPred		0.96		Gain of catalytic residue at M1 (P = 0.0099);
MVP		0.99
ClinPred		0.99	D
GERP RS		2.5
PromoterAI		-0.10	Neutral
Varity_R		0.85
gMVP		0.91
Mutation Taster		=45/155	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs930701747; hg19: chr13-96205009;