Variant 1-151518685-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_020770.3(CGN):c.166C>T(p.Arg56Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,984 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 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

CGN
NM_020770.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.89

Variant links:

Genes affected

CGN (HGNC:17429): (cingulin) Enables cadherin binding activity. Predicted to act upstream of or within bicellular tight junction assembly; epithelial cell morphogenesis; and microtubule cytoskeleton organization. Located in bicellular tight junction and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CGN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.862

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CGN	NM_020770.3 link	c.166C>T	p.Arg56Cys	missense_variant	Exon 2 of 21	ENST00000271636.12	NP_065821.1	Q9P2M7-1
CGN	XM_005245365.6 link	c.166C>T	p.Arg56Cys	missense_variant	Exon 2 of 21		XP_005245422.1	Q9P2M7-1
CGN	XR_921902.3 link	n.309C>T		non_coding_transcript_exon_variant	Exon 2 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CGN	ENST00000271636.12 link	c.166C>T	p.Arg56Cys	missense_variant	Exon 2 of 21	1	NM_020770.3	ENSP00000271636.7	Q9P2M7-1
CGN	ENST00000502442.1 link	c.166C>T	p.Arg56Cys	missense_variant	Exon 2 of 2	1		ENSP00000422299.1	A2A3M4
CGN	ENST00000505188.5 link	c.166C>T	p.Arg56Cys	missense_variant	Exon 2 of 2	1		ENSP00000425532.1	A2A3M4
CGN	ENST00000427934.2 link	c.166C>T	p.Arg56Cys	missense_variant	Exon 3 of 3	5		ENSP00000410836.1	A6PVU7

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251408

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152098

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.166C>T (p.R56C) alteration is located in exon 2 (coding exon 1) of the CGN gene. This alteration results from a C to T substitution at nucleotide position 166, causing the arginine (R) at amino acid position 56 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.40

BayesDel_noAF

Pathogenic

0.42

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.34

.;.;T;.

Eigen

Pathogenic

0.69

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Uncertain

0.90

LIST_S2

Pathogenic

0.97

.;D;D;.

M_CAP

Uncertain

0.17

MetaRNN

Pathogenic

0.86

D;D;D;D

MetaSVM

Uncertain

0.75

PrimateAI

Pathogenic

0.93

PROVEAN

Pathogenic

-8.0

D;D;D;D

REVEL

Pathogenic

0.77

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D

Vest4

0.90

MVP

0.77

MPC

0.76

ClinPred

1.0

GERP RS

5.1

gMVP

0.59

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over