13-95553079-C-T

Position:

• chr13-95553079-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006984.5(CLDN10):​c.220+106C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 1,430,694 control chromosomes in the GnomAD database, including 18,864 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1448 hom., cov: 33)
  • Exomes 𝑓: 0.16 (17416 hom.)
• Consequence: CLDN10 NM_006984.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0180

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 13-95553079-C-T is Benign according to our data. Variant chr13-95553079-C-T is described in ClinVar as [Benign]. Clinvar id is 1278746.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLDN10	NM_006984.5	c.220+106C>T		intron_variant		ENST00000299339.3	NP_008915.1
CLDN10	XM_047430765.1	c.-2926C>T		5_prime_UTR_variant	1/6		XP_047286721.1
CLDN10	NM_182848.4	c.215-7053C>T		intron_variant			NP_878268.1
CLDN10	NM_001160100.2	c.158-7053C>T		intron_variant			NP_001153572.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLDN10	ENST00000299339.3	c.220+106C>T		intron_variant		1	NM_006984.5	ENSP00000299339.2
CLDN10	ENST00000376873.7	c.215-7053C>T		intron_variant		2		ENSP00000366069.2

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17732 AN: 152038 Hom.: 1442 Cov.: 33

Gnomad AFR AF: 0.0311

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.0723

Gnomad EAS AF: 0.00407

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.112

GnomAD4 exome AF: 0.158 AC: 201462 AN: 1278538 Hom.: 17416 AF XY: 0.157 AC XY: 98340 AN XY: 628092

Gnomad4 AFR exome AF: 0.0224

Gnomad4 AMR exome AF: 0.271

Gnomad4 ASJ exome AF: 0.0672

Gnomad4 EAS exome AF: 0.00372

Gnomad4 SAS exome AF: 0.140

Gnomad4 FIN exome AF: 0.163

Gnomad4 NFE exome AF: 0.168

Gnomad4 OTH exome AF: 0.134

GnomAD4 genome AF: 0.117 AC: 17748 AN: 152156 Hom.: 1448 Cov.: 33 AF XY: 0.117 AC XY: 8691 AN XY: 74378

Gnomad4 AFR AF: 0.0310

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.0723

Gnomad4 EAS AF: 0.00408

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.111

Alfa AF: 0.0671 Hom.: 93

Bravo AF: 0.119

Asia WGS AF: 0.0580 AC: 202 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.1
DANN	Benign	0.85

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

Other links and lift over

dbSNP: rs113108501; hg19: chr13-96205333;