rs763080763

Variant names:

• chr17-7261961-G-A
• rs763080763
• NM_001307.6:c.83C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-7261961-G-A
• chr17-7261961-G-C

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001307.6(CLDN7):​c.83C>T​(p.Pro28Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,716 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: CLDN7 NM_001307.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.89
• Publications: 0 publications found

Genes affected

CLDN7 (HGNC:2049): (claudin 7) 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. Differential expression of this gene has been observed in different types of malignancies, including breast cancer, ovarian cancer, hepatocellular carcinomas, urinary tumors, prostate cancer, lung cancer, head and neck cancers, thyroid carcinomas, etc.. Alternatively spliced transcript variants encoding different isoforms have been found.[provided by RefSeq, May 2010]

ENSG00000262302 (HGNC:):

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.94

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001307.6. 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
	CLDN7	NM_001307.6	MANE Select	c.83C>T	p.Pro28Leu	missense	Exon 1 of 4	NP_001298.3
	CLDN7	NM_001185022.2		c.83C>T	p.Pro28Leu	missense	Exon 2 of 5	NP_001171951.1	A0A384ME58
	CLDN7	NM_001185023.2		c.83C>T	p.Pro28Leu	missense	Exon 1 of 3	NP_001171952.1	F5H496

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN7	ENST00000360325.11	TSL:1 MANE Select	c.83C>T	p.Pro28Leu	missense	Exon 1 of 4	ENSP00000353475.7	O95471-1
	CLDN7	ENST00000397317.8	TSL:1	c.83C>T	p.Pro28Leu	missense	Exon 2 of 5	ENSP00000396638.3	O95471-1
	ENSG00000262302	ENST00000577138.1	TSL:3	n.83C>T		non_coding_transcript_exon	Exon 1 of 4	ENSP00000460571.1	I3L3M4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000159 AC: 4 AN: 250810 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000353

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000109 AC: 16 AN: 1461716 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727144

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53306

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1111996

Other (OTH) AF: 0.0000166 AC: 1 AN: 60392

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.43
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.94	D
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.90	D
M_CAP	Pathogenic	0.50	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Pathogenic	0.91	D
MutationAssessor	Pathogenic	4.0	H
PhyloP100		9.9
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-8.7	D
REVEL	Pathogenic	0.86
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.93
MutPred		0.76		Gain of catalytic residue at P28 (P = 0.0065)
MVP		0.97
MPC		0.53
ClinPred		0.99	D
GERP RS		4.0
PromoterAI		0.073	Neutral
Varity_R		0.86
gMVP		0.78
Mutation Taster		=60/40	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: rs763080763; hg19: chr17-7165280;