chr13-95560139-A-C

Variant names:

• chr13-95560139-A-C
• rs34449921
• NM_006984.5:c.228A>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BS1 BS2

The NM_006984.5(CLDN10):​c.228A>C​(p.Ile76Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00167 in 1,612,620 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0089 (23 hom., cov: 33)
  • Exomes 𝑓: 0.00092 (20 hom.)
• Consequence: CLDN10 NM_006984.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.10
• Publications: 3 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 13-95560139-A-C is Benign according to our data. Variant chr13-95560139-A-C is described in ClinVar as Benign. ClinVar VariationId is 3044485.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=1.1 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00888 (1353/152354) while in subpopulation AFR AF = 0.031 (1290/41584). AF 95% confidence interval is 0.0296. There are 23 homozygotes in GnomAd4. There are 652 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 23 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006984.5. 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_006984.5	MANE Select	c.228A>C	p.Ile76Ile	synonymous	Exon 2 of 5	NP_008915.1	P78369-1
	CLDN10	NM_182848.4		c.222A>C	p.Ile74Ile	synonymous	Exon 2 of 5	NP_878268.1	P78369-2
	CLDN10	NM_001160100.2		c.165A>C	p.Ile55Ile	synonymous	Exon 2 of 5	NP_001153572.1	P78369-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN10	ENST00000299339.3	TSL:1 MANE Select	c.228A>C	p.Ile76Ile	synonymous	Exon 2 of 5	ENSP00000299339.2	P78369-1
	CLDN10	ENST00000905060.1		c.318A>C	p.Ile106Ile	synonymous	Exon 3 of 6	ENSP00000575119.1
	CLDN10	ENST00000376873.7	TSL:2	c.222A>C	p.Ile74Ile	synonymous	Exon 2 of 5	ENSP00000366069.2	P78369-2

Frequencies

GnomAD3 genomes AF: 0.00883 AC: 1344 AN: 152236 Hom.: 23 Cov.: 33

Gnomad AFR AF: 0.0309

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00268

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00669

GnomAD2 exomes AF: 0.00226 AC: 566 AN: 250698 AF XY: 0.00173

Gnomad AFR exome AF: 0.0300

Gnomad AMR exome AF: 0.00169

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000705

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.000921 AC: 1345 AN: 1460266 Hom.: 20 Cov.: 31 AF XY: 0.000819 AC XY: 595 AN XY: 726186

African (AFR) AF: 0.0319 AC: 1064 AN: 33380

American (AMR) AF: 0.00166 AC: 74 AN: 44542

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26094

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86036

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00174 AC: 10 AN: 5762

European-Non Finnish (NFE) AF: 0.0000522 AC: 58 AN: 1111052

Other (OTH) AF: 0.00214 AC: 129 AN: 60328

GnomAD4 genome AF: 0.00888 AC: 1353 AN: 152354 Hom.: 23 Cov.: 33 AF XY: 0.00875 AC XY: 652 AN XY: 74506

African (AFR) AF: 0.0310 AC: 1290 AN: 41584

American (AMR) AF: 0.00268 AC: 41 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68024

Other (OTH) AF: 0.00662 AC: 14 AN: 2116

Alfa AF: 0.00381 Hom.: 7

Bravo AF: 0.00958

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CLDN10-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	13
DANN	Benign	0.70
PhyloP100		1.1
PromoterAI		0.020	Neutral
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs34449921; hg19: chr13-96212393;