13-95433626-C-T

Variant names:

• chr13-95433626-C-T
• rs115306504
• ENST00000376873.7:c.-208C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000376873.7(CLDN10):​c.-208C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000258 in 387,318 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000026 (0 hom.)
• Consequence: CLDN10 ENST00000376873.7 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0970
• Publications: 0 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: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000376873.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN10	NM_182848.4		c.-208C>T		upstream_gene	N/A	NP_878268.1	P78369-2
	CLDN10	NM_001160100.2		c.-208C>T		upstream_gene	N/A	NP_001153572.1	P78369-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN10	ENST00000376873.7	TSL:2	c.-208C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000366069.2	P78369-2
	CLDN10	ENST00000376873.7	TSL:2	c.-208C>T		5_prime_UTR	Exon 1 of 5	ENSP00000366069.2	P78369-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000258 AC: 1 AN: 387318 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 201104

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 11234

American (AMR) AF: 0.00 AC: 0 AN: 14830

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12382

East Asian (EAS) AF: 0.00 AC: 0 AN: 28094

South Asian (SAS) AF: 0.00 AC: 0 AN: 32812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26788

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1724

European-Non Finnish (NFE) AF: 0.00000423 AC: 1 AN: 236220

Other (OTH) AF: 0.00 AC: 0 AN: 23234

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Benign	0.58
PhyloP100		-0.097
PromoterAI		-0.035	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs115306504; hg19: chr13-96085880;