Variant 19-43625111-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_145296.2(CADM4):c.895C>T(p.His299Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,610,792 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: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CADM4
NM_145296.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.16

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:

LOC105372411 (HGNC:):

LOC105372411 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.250511).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CADM4	NM_145296.2 linkuse as main transcript	c.895C>T	p.His299Tyr	missense_variant	7/9	ENST00000222374.3	NP_660339.1
LOC105372411	XR_001753942.2 linkuse as main transcript	n.573-3673G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CADM4	ENST00000222374.3 linkuse as main transcript	c.895C>T	p.His299Tyr	missense_variant	7/9	1	NM_145296.2	ENSP00000222374	P1
CADM4	ENST00000593506.1 linkuse as main transcript	n.201C>T		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes

AF:

0.0000133

AC:

AN:

150730

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000490

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460062

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726322

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

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:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000133

AC:

AN:

150730

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73442

show subpopulations

Gnomad4 AFR

AF:

0.0000490

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 06, 2023

The c.895C>T (p.H299Y) alteration is located in exon 7 (coding exon 7) of the CADM4 gene. This alteration results from a C to T substitution at nucleotide position 895, causing the histidine (H) at amino acid position 299 to be replaced by a tyrosine (Y). 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

0.15

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.040

Eigen

Benign

0.0042

Eigen_PC

Benign

0.20

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.82

M_CAP

Benign

0.0070

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.045

MutationTaster

Benign

0.95

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.87

REVEL

Benign

0.072

Sift

Benign

0.043

Sift4G

Uncertain

0.041

Polyphen

0.30

Vest4

0.31

MVP

0.18

MPC

1.2

ClinPred

0.78

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.64

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