chr13-95553105-A-C

Position:

• chr13-95553105-A-C

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+132A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.998 in 1,273,632 control chromosomes in the GnomAD database, including 634,101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.99 (74490 hom., cov: 30)
  • Exomes 𝑓: 1.0 (559611 hom.)
• Consequence: CLDN10 NM_006984.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0730

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=-0.89).
• BP6: Variant 13-95553105-A-C is Benign according to our data. Variant chr13-95553105-A-C is described in ClinVar as [Benign]. Clinvar id is 1240911.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLDN10	NM_006984.5	c.220+132A>C		intron_variant		ENST00000299339.3	NP_008915.1
CLDN10	XM_047430765.1	c.-2900A>C		5_prime_UTR_variant	1/6		XP_047286721.1
CLDN10	NM_182848.4	c.215-7027A>C		intron_variant			NP_878268.1
CLDN10	NM_001160100.2	c.158-7027A>C		intron_variant			NP_001153572.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLDN10	ENST00000299339.3	c.220+132A>C		intron_variant		1	NM_006984.5	ENSP00000299339.2
CLDN10	ENST00000376873.7	c.215-7027A>C		intron_variant		2		ENSP00000366069.2

Frequencies

GnomAD3 genomes AF: 0.989 AC: 150424 AN: 152050 Hom.: 74435 Cov.: 30

Gnomad AFR AF: 0.962

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.997

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.996

GnomAD4 exome AF: 0.999 AC: 1120329 AN: 1121464 Hom.: 559611 AF XY: 0.999 AC XY: 552928 AN XY: 553420

Gnomad4 AFR exome AF: 0.965

Gnomad4 AMR exome AF: 0.998

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.998

GnomAD4 genome AF: 0.989 AC: 150538 AN: 152168 Hom.: 74490 Cov.: 30 AF XY: 0.989 AC XY: 73595 AN XY: 74392

Gnomad4 AFR AF: 0.962

Gnomad4 AMR AF: 0.997

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 1.00

Gnomad4 OTH AF: 0.996

Alfa AF: 1.00 Hom.: 3328

Bravo AF: 0.989

Asia WGS AF: 0.998 AC: 3472 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 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.2
DANN	Benign	0.54

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: rs1886855; hg19: chr13-96205359;