Variant chr1-159196392-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001127173.3(CADM3):c.720C>A(p.Asp240Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000564 in 1,614,002 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00059 ( 1 hom. )

Consequence

CADM3
NM_001127173.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.208

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:

CADM3-AS1 (HGNC:40812): (CADM3 antisense RNA 1)

CADM3-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.018955082).

BS2

High AC in GnomAd4 at 46 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CADM3	NM_001127173.3 linkuse as main transcript	c.720C>A	p.Asp240Glu	missense_variant	6/9	ENST00000368125.9	NP_001120645.1
CADM3-AS1	NR_037870.1 linkuse as main transcript	n.2887G>T		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CADM3	ENST00000368125.9 linkuse as main transcript	c.720C>A	p.Asp240Glu	missense_variant	6/9	1	NM_001127173.3	ENSP00000357107	P2	Q8N126-1
CADM3	ENST00000368124.8 linkuse as main transcript	c.822C>A	p.Asp274Glu	missense_variant	7/10	1		ENSP00000357106	A2	Q8N126-2
CADM3	ENST00000416746.1 linkuse as main transcript	c.582C>A	p.Asp194Glu	missense_variant	6/7	1		ENSP00000387802
CADM3-AS1	ENST00000415675.3 linkuse as main transcript	n.2977G>T		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes

AF:

0.000302

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000529

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000306

AC:

AN:

251402

Hom.:

AF XY:

0.000302

AC XY:

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.000246

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:

0.000624

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000591

AC:

864

AN:

1461836

Hom.:

Cov.:

AF XY:

0.000550

AC XY:

400

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000743

Gnomad4 OTH exome

AF:

0.000480

GnomAD4 genome

AF:

0.000302

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.000283

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000529

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000570

Hom.:

Bravo

AF:

0.000344

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000272

AC:

EpiCase

AF:

0.000763

EpiControl

AF:

0.000652

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

Jun 27, 2022

The c.822C>A (p.D274E) alteration is located in exon 7 (coding exon 7) of the CADM3 gene. This alteration results from a C to A substitution at nucleotide position 822, causing the aspartic acid (D) at amino acid position 274 to be replaced by a glutamic acid (E). 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

0.10

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.79

DEOGEN2

Benign

0.057

.;T;.

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.62

T;T;T

M_CAP

Benign

0.0044

MetaRNN

Benign

0.019

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.32

.;N;.

MutationTaster

Benign

0.98

N;N

PrimateAI

Benign

0.38

PROVEAN

Benign

0.090

N;N;N

REVEL

Benign

0.020

Sift

Benign

0.77

T;T;T

Sift4G

Benign

0.51

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.089

MutPred

0.21

.;Gain of sheet (P = 0.0827);.;

MVP

0.25

MPC

0.38

ClinPred

0.0096

GERP RS

1.6

Varity_R

0.029

gMVP

0.49

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