rs201650771

Variant names:

• chr7-73769827-C-G
• rs201650771
• NM_001306.4:c.223G>C

Your query was ambiguous. Multiple possible variants found:

• chr7-73769827-C-G
• chr7-73769827-C-A
• chr7-73769827-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001306.4(CLDN3):​c.223G>C​(p.Asp75His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000533 in 1,612,420 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: 𝑓 0.000053 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000053 (0 hom.)
• Consequence: CLDN3 NM_001306.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.86
• Publications: 0 publications found

Genes affected

CLDN3 (HGNC:2045): (claudin 3) Tight junctions represent one mode of cell-to-cell adhesion in epithelial or endothelial cell sheets, forming continuous seals around cells and serving as a physical barrier to prevent solutes and water from passing freely through the paracellular space. These junctions are comprised of sets of continuous networking strands in the outwardly facing cytoplasmic leaflet, with complementary grooves in the inwardly facing extracytoplasmic leaflet. The protein encoded by this intronless gene, a member of the claudin family, is an integral membrane protein and a component of tight junction strands. It is also a low-affinity receptor for Clostridium perfringens enterotoxin, and shares aa sequence similarity with a putative apoptosis-related protein found in rat. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.769

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001306.4. 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
	CLDN3	NM_001306.4	MANE Select	c.223G>C	p.Asp75His	missense	Exon 1 of 1	NP_001297.1	Q75L79

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN3	ENST00000395145.3	TSL:6 MANE Select	c.223G>C	p.Asp75His	missense	Exon 1 of 1	ENSP00000378577.2	O15551

Frequencies

GnomAD3 genomes AF: 0.0000525 AC: 8 AN: 152260 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000104 AC: 26 AN: 250140 AF XY: 0.0000886

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: 0.000556

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.000328

GnomAD4 exome AF: 0.0000534 AC: 78 AN: 1460160 Hom.: 0 Cov.: 31 AF XY: 0.0000496 AC XY: 36 AN XY: 726406

African (AFR) AF: 0.00 AC: 0 AN: 33428

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86166

European-Finnish (FIN) AF: 0.000714 AC: 38 AN: 53232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4674

European-Non Finnish (NFE) AF: 0.0000324 AC: 36 AN: 1111864

Other (OTH) AF: 0.0000664 AC: 4 AN: 60268

GnomAD4 genome AF: 0.0000525 AC: 8 AN: 152260 Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6 AN XY: 74386

African (AFR) AF: 0.00 AC: 0 AN: 41472

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.000659 AC: 7 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.000173 AC: 21

ClinVar

ClinVar submissions

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	0.92
BayesDel_addAF	Uncertain	0.065	T
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	32
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.65	D
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.89	D
M_CAP	Uncertain	0.17	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Uncertain	0.58	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		7.9
PrimateAI	Pathogenic	0.81	D
PROVEAN	Pathogenic	-6.5	D
REVEL	Uncertain	0.64
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.021	D
Polyphen		1.0	D
Vest4		0.76
MVP		0.94
MPC		1.8
ClinPred		0.38	T
GERP RS		4.0
PromoterAI		-0.025	Neutral
Varity_R		0.89
gMVP		0.95
Mutation Taster		=40/60	disease causing

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: rs201650771; hg19: chr7-73184157;