19-43626251-G-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_145296.2(CADM4):ā€‹c.537C>Gā€‹(p.Ser179Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,460,556 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 (ā˜…).

Frequency

Genomes: not found (cov: 31)
Exomes š‘“: 0.0000048 ( 0 hom. )

Consequence

CADM4
NM_145296.2 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.495
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.19768506).
BS2
High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CADM4NM_145296.2 linkuse as main transcriptc.537C>G p.Ser179Arg missense_variant 5/9 ENST00000222374.3 NP_660339.1 Q8NFZ8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CADM4ENST00000222374.3 linkuse as main transcriptc.537C>G p.Ser179Arg missense_variant 5/91 NM_145296.2 ENSP00000222374.1 Q8NFZ8

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000400
AC:
1
AN:
250170
Hom.:
0
AF XY:
0.00000739
AC XY:
1
AN XY:
135356
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:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1460556
Hom.:
0
Cov.:
32
AF XY:
0.00000688
AC XY:
5
AN XY:
726678
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:
0.00
Gnomad4 NFE exome
AF:
0.00000630
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
ExAC
AF:
0.00000824
AC:
1

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 submitterclinical testingAmbry GeneticsApr 05, 2023The c.537C>G (p.S179R) alteration is located in exon 5 (coding exon 5) of the CADM4 gene. This alteration results from a C to G substitution at nucleotide position 537, causing the serine (S) at amino acid position 179 to be replaced by an arginine (R). 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
Uncertain
0.44
BayesDel_addAF
Benign
-0.066
T
BayesDel_noAF
Benign
-0.33
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.25
T
Eigen
Benign
-0.56
Eigen_PC
Benign
-0.44
FATHMM_MKL
Benign
0.60
D
LIST_S2
Benign
0.78
T
M_CAP
Uncertain
0.086
D
MetaRNN
Benign
0.20
T
MetaSVM
Benign
-0.80
T
MutationAssessor
Uncertain
2.2
M
MutationTaster
Benign
0.98
D
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-2.1
N
REVEL
Benign
0.23
Sift
Benign
0.037
D
Sift4G
Uncertain
0.0040
D
Polyphen
0.0010
B
Vest4
0.27
MutPred
0.62
Gain of MoRF binding (P = 0.0407);
MVP
0.25
MPC
1.1
ClinPred
0.25
T
GERP RS
0.89
Varity_R
0.27
gMVP
0.83

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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.

Other links and lift over

dbSNP: rs762172694; hg19: chr19-44130403; API