chr13-95433626-C-A

Position:

• chr13-95433626-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000376873(CLDN10):​c.-208C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00749 in 539,550 control chromosomes in the GnomAD database, including 119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (99 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (20 hom.)
• Consequence: CLDN10 ENST00000376873 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0970

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 13-95433626-C-A is Benign according to our data. Variant chr13-95433626-C-A is described in ClinVar as [Benign]. Clinvar id is 1268459.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.95433626C>A		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLDN10	ENST00000376873	c.-208C>A		5_prime_UTR_variant	1/5	2		ENSP00000366069.2

Frequencies

GnomAD3 genomes AF: 0.0190 AC: 2885 AN: 152130 Hom.: 95 Cov.: 32

Gnomad AFR AF: 0.0642

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00917

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000691

Gnomad OTH AF: 0.0153

GnomAD4 exome AF: 0.00295 AC: 1141 AN: 387302 Hom.: 20 Cov.: 4 AF XY: 0.00257 AC XY: 517 AN XY: 201092

Gnomad4 AFR exome AF: 0.0610

Gnomad4 AMR exome AF: 0.00674

Gnomad4 ASJ exome AF: 0.000565

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000183

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000711

Gnomad4 OTH exome AF: 0.00684

GnomAD4 genome AF: 0.0191 AC: 2901 AN: 152248 Hom.: 99 Cov.: 32 AF XY: 0.0184 AC XY: 1371 AN XY: 74424

Gnomad4 AFR AF: 0.0644

Gnomad4 AMR AF: 0.00916

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000691

Gnomad4 OTH AF: 0.0151

Alfa AF: 0.0116 Hom.: 8

Bravo AF: 0.0214

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 20, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.8
DANN	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs115306504; hg19: chr13-96085880;