Variant rs193920866 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_001127173.3(CADM3):c.382G>A(p.Gly128Arg) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 14/25 in silico tools predict a damaging outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CADM3
NM_001127173.3 missense, splice_region

Scores

Splicing: ADA: 1.000

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.41

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:

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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, 0.847

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CADM3	NM_001127173.3 linkuse as main transcript	c.382G>A	p.Gly128Arg	missense_variant, splice_region_variant	3/9	ENST00000368125.9	NP_001120645.1
CADM3	NM_021189.5 linkuse as main transcript	c.484G>A	p.Gly162Arg	missense_variant, splice_region_variant	4/10		NP_067012.1
CADM3	NM_001346510.2 linkuse as main transcript	c.382G>A	p.Gly128Arg	missense_variant, splice_region_variant	3/9		NP_001333439.1
CADM3	XM_024448760.2 linkuse as main transcript	c.631G>A	p.Gly211Arg	missense_variant, splice_region_variant	6/12		XP_024304528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CADM3	ENST00000368125.9 linkuse as main transcript	c.382G>A	p.Gly128Arg	missense_variant, splice_region_variant	3/9	1	NM_001127173.3	ENSP00000357107	P2	Q8N126-1
CADM3	ENST00000368124.8 linkuse as main transcript	c.484G>A	p.Gly162Arg	missense_variant, splice_region_variant	4/10	1		ENSP00000357106	A2	Q8N126-2
CADM3	ENST00000416746.1 linkuse as main transcript	c.382G>A	p.Gly128Arg	missense_variant, splice_region_variant	3/7	1		ENSP00000387802

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

249976

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135050

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

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:

0.00000206

AC:

AN:

1458808

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725198

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Pathogenic

0.31

BayesDel_noAF

Pathogenic

0.38

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.35

.;T;.

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Uncertain

0.10

MetaRNN

Pathogenic

0.85

D;D;D

MetaSVM

Uncertain

0.22

MutationAssessor

Pathogenic

3.0

.;M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.79

PROVEAN

Uncertain

-3.6

D;D;D

REVEL

Pathogenic

0.77

Sift

Benign

0.068

T;D;D

Sift4G

Benign

0.16

T;T;D

Polyphen

1.0

D;D;.

Vest4

0.85

MutPred

0.60

.;Gain of MoRF binding (P = 0.0022);Gain of MoRF binding (P = 0.0022);

MVP

0.93

MPC

1.1

ClinPred

0.97

GERP RS

5.1

Varity_R

0.73

gMVP

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

1.0

SpliceAI score (max)

0.27

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.27

Position offset: 0

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over