rs3751334

Variant names:

• chr13-95433756-A-G
• rs3751334
• NM_182848.4:c.-78A>G

Your query was ambiguous. Multiple possible variants found:

• chr13-95433756-A-G
• chr13-95433756-A-C
• chr13-95433756-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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 -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182848.4. 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_182848.4		c.-78A>G		5_prime_UTR	Exon 1 of 5	NP_878268.1	P78369-2
	CLDN10	NM_001160100.2		c.-78A>G		5_prime_UTR	Exon 1 of 5	NP_001153572.1	P78369-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN10	ENST00000376873.7	TSL:2	c.-78A>G		5_prime_UTR	Exon 1 of 5	ENSP00000366069.2	P78369-2

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

African (AFR) AF: 0.0844 AC: 2600 AN: 30790

American (AMR) AF: 0.192 AC: 8087 AN: 42218

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 2605 AN: 24818

East Asian (EAS) AF: 0.169 AC: 6480 AN: 38242

South Asian (SAS) AF: 0.136 AC: 11099 AN: 81562

European-Finnish (FIN) AF: 0.164 AC: 8572 AN: 52404

Middle Eastern (MID) AF: 0.182 AC: 710 AN: 3908

European-Non Finnish (NFE) AF: 0.142 AC: 140547 AN: 991412

Other (OTH) AF: 0.143 AC: 7936 AN: 55452

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

African (AFR) AF: 0.0838 AC: 3478 AN: 41528

American (AMR) AF: 0.180 AC: 2751 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 365 AN: 3472

East Asian (EAS) AF: 0.138 AC: 714 AN: 5172

South Asian (SAS) AF: 0.128 AC: 616 AN: 4822

European-Finnish (FIN) AF: 0.168 AC: 1781 AN: 10600

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9636 AN: 67984

Other (OTH) AF: 0.124 AC: 263 AN: 2114

Alfa AF: 0.137 Hom.: 783

Bravo AF: 0.127

Asia WGS AF: 0.134 AC: 463 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.34
DANN	Benign	0.53
PhyloP100		-0.44
PromoterAI		0.055	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3751334; hg19: chr13-96086010;