Genetic Variant CADM4:p.Ala4Pro (chr19-43639781-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_145296.2(CADM4):c.10G>C(p.Ala4Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A4T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 27)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CADM4
NM_145296.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.08

Publications

0 publications found

Variant links:

Genes affected

CADM4 (HGNC:30825): (cell adhesion molecule 4) Enables vascular endothelial growth factor receptor 2 binding activity. Involved in several processes, including negative regulation of protein phosphorylation; regulation of Rac protein signal transduction; and regulation of wound healing. Located in cell leading edge and cell-cell contact zone. [provided by Alliance of Genome Resources, Apr 2022]

CADM4 links:

ENSG00000308028 (HGNC:):

ENSG00000308028 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16507638).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145296.2. 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
	CADM4	NM_145296.2	MANE Select	c.10G>C	p.Ala4Pro	missense	Exon 1 of 9	NP_660339.1	Q8NFZ8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CADM4	ENST00000222374.3	TSL:1 MANE Select	c.10G>C	p.Ala4Pro	missense	Exon 1 of 9	ENSP00000222374.1	Q8NFZ8
CADM4	ENST00000904152.1		c.10G>C	p.Ala4Pro	missense	Exon 1 of 10	ENSP00000574211.1
CADM4	ENST00000904153.1		c.10G>C	p.Ala4Pro	missense	Exon 1 of 9	ENSP00000574212.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

871434

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

411158

African (AFR)

AF:

0.00

AC:

AN:

16350

American (AMR)

AF:

0.00

AC:

AN:

4160

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

6344

East Asian (EAS)

AF:

0.00

AC:

AN:

4430

South Asian (SAS)

AF:

0.00

AC:

AN:

22806

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1348

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1746

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

785478

Other (OTH)

AF:

0.00

AC:

AN:

28772

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.085

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0013

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.44

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

2.1

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.73

REVEL

Benign

0.083

Sift

Benign

0.25

Sift4G

Pathogenic

0.0

Polyphen

0.62

Vest4

0.27

MutPred

0.42

Gain of glycosylation at A4 (P = 0.01)

MVP

0.60

MPC

2.0

ClinPred

0.41

GERP RS

1.5

PromoterAI

-0.10

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.14

gMVP

0.61

Mutation Taster

=84/16

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over