13-95433756-A-G

Position:

• chr13-95433756-A-G

Variant summary

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

The NM_182848.4(CLDN10):​c.-78A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,472,970 control chromosomes in the GnomAD database, including 15,295 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1391 hom., cov: 32)
  • Exomes 𝑓: 0.14 (13904 hom.)
• Consequence: CLDN10 NM_182848.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.438

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 13-95433756-A-G is Benign according to our data. Variant chr13-95433756-A-G is described in ClinVar as [Benign]. Clinvar id is 1283407.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLDN10	NM_182848.4	c.-78A>G		5_prime_UTR_variant	1/5		NP_878268.1
CLDN10	NM_001160100.2	c.-78A>G		5_prime_UTR_variant	1/5		NP_001153572.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLDN10	ENST00000376873	c.-78A>G		5_prime_UTR_variant	1/5	2		ENSP00000366069.2

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19677 AN: 152046 Hom.: 1389 Cov.: 32

Gnomad AFR AF: 0.0836

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.123

GnomAD4 exome AF: 0.143 AC: 188636 AN: 1320806 Hom.: 13904 Cov.: 19 AF XY: 0.143 AC XY: 94208 AN XY: 660822

Gnomad4 AFR exome AF: 0.0844

Gnomad4 AMR exome AF: 0.192

Gnomad4 ASJ exome AF: 0.105

Gnomad4 EAS exome AF: 0.169

Gnomad4 SAS exome AF: 0.136

Gnomad4 FIN exome AF: 0.164

Gnomad4 NFE exome AF: 0.142

Gnomad4 OTH exome AF: 0.143

GnomAD4 genome AF: 0.129 AC: 19698 AN: 152164 Hom.: 1391 Cov.: 32 AF XY: 0.132 AC XY: 9815 AN XY: 74388

Gnomad4 AFR AF: 0.0838

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.124

Alfa AF: 0.138 Hom.: 712

Bravo AF: 0.127

Asia WGS AF: 0.134 AC: 463 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 10, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.34
DANN	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3751334; hg19: chr13-96086010;