rs9302082

Variant names:

• chr13-95564649-A-G
• rs9302082
• NM_006984.5:c.464+4186A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006984.5(CLDN10):​c.464+4186A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,150 control chromosomes in the GnomAD database, including 4,019 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (4019 hom., cov: 32)
• Consequence: CLDN10 NM_006984.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.609
• Publications: 4 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: Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLDN10	NM_006984.5	c.464+4186A>G		intron_variant	Intron 3 of 4	ENST00000299339.3	NP_008915.1
CLDN10	NM_182848.4	c.458+4186A>G		intron_variant	Intron 3 of 4		NP_878268.1
CLDN10	NM_001160100.2	c.401+4186A>G		intron_variant	Intron 3 of 4		NP_001153572.1
CLDN10	XM_047430765.1	c.290+4186A>G		intron_variant	Intron 4 of 5		XP_047286721.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLDN10	ENST00000299339.3	c.464+4186A>G		intron_variant	Intron 3 of 4	1	NM_006984.5	ENSP00000299339.2
CLDN10	ENST00000376873.7	c.458+4186A>G		intron_variant	Intron 3 of 4	2		ENSP00000366069.2

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33537 AN: 152032 Hom.: 4005 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.247

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.221 AC: 33577 AN: 152150 Hom.: 4019 Cov.: 32 AF XY: 0.225 AC XY: 16701 AN XY: 74376

African (AFR) AF: 0.160 AC: 6650 AN: 41524

American (AMR) AF: 0.329 AC: 5031 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 931 AN: 3470

East Asian (EAS) AF: 0.267 AC: 1380 AN: 5164

South Asian (SAS) AF: 0.311 AC: 1500 AN: 4828

European-Finnish (FIN) AF: 0.227 AC: 2404 AN: 10582

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14604 AN: 67984

Other (OTH) AF: 0.255 AC: 538 AN: 2112

Alfa AF: 0.223 Hom.: 11401

Bravo AF: 0.227

Asia WGS AF: 0.324 AC: 1128 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.058
DANN	Benign	0.32
PhyloP100		-0.61
Mutation Taster		=100/0	polymorphism (auto)

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: rs9302082; hg19: chr13-96216903;