Variant chr1-159193467-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001127173.3(CADM3):c.427C>T(p.Arg143Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000048 in 1,459,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

CADM3
NM_001127173.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.576

Variant links:

Genes affected

CADM3 (HGNC:17601): (cell adhesion molecule 3) The protein encoded by this gene is a calcium-independent cell-cell adhesion protein that can form homodimers or heterodimers with other nectin proteins. The encoded protein has both homophilic and heterophilic cell-cell adhesion activity. This gene is reported to be a tumor suppressor gene. [provided by RefSeq, Oct 2016]

CADM3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3425858).

BS2

High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CADM3	NM_001127173.3 linkuse as main transcript	c.427C>T	p.Arg143Trp	missense_variant	4/9	ENST00000368125.9	NP_001120645.1
CADM3	NM_021189.5 linkuse as main transcript	c.529C>T	p.Arg177Trp	missense_variant	5/10		NP_067012.1
CADM3	NM_001346510.2 linkuse as main transcript	c.427C>T	p.Arg143Trp	missense_variant	4/9		NP_001333439.1
CADM3	XM_024448760.2 linkuse as main transcript	c.676C>T	p.Arg226Trp	missense_variant	7/12		XP_024304528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CADM3	ENST00000368125.9 linkuse as main transcript	c.427C>T	p.Arg143Trp	missense_variant	4/9	1	NM_001127173.3	ENSP00000357107	P2	Q8N126-1
CADM3	ENST00000368124.8 linkuse as main transcript	c.529C>T	p.Arg177Trp	missense_variant	5/10	1		ENSP00000357106	A2	Q8N126-2
CADM3	ENST00000416746.1 linkuse as main transcript	c.427C>T	p.Arg143Trp	missense_variant	4/7	1		ENSP00000387802

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250580

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135420

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000480

AC:

AN:

1459720

Hom.:

Cov.:

AF XY:

0.00000689

AC XY:

AN XY:

725766

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 17, 2023

The c.529C>T (p.R177W) alteration is located in exon 5 (coding exon 5) of the CADM3 gene. This alteration results from a C to T substitution at nucleotide position 529, causing the arginine (R) at amino acid position 177 to be replaced by a tryptophan (W). 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

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.0018

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.53

.;D;.

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Benign

0.16

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Uncertain

0.087

MetaRNN

Benign

0.34

T;T;T

MetaSVM

Uncertain

-0.26

MutationAssessor

Benign

1.9

.;L;.

MutationTaster

Benign

0.87

D;D

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.6

N;N;N

REVEL

Uncertain

0.40

Sift

Uncertain

0.018

D;D;D

Sift4G

Uncertain

0.018

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.28

MutPred

0.53

.;Loss of disorder (P = 0.013);Loss of disorder (P = 0.013);

MVP

0.51

MPC

1.2

ClinPred

0.88

GERP RS

5.1

Varity_R

0.099

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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