1-159171824-C-G

Variant names:

• chr1-159171824-C-G
• NM_001127173.3:c.59C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001127173.3(CADM3):​c.59C>G​(p.Ala20Gly) 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A20S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CADM3 NM_001127173.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.25

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]

AIM2 (HGNC:357): (absent in melanoma 2) AIM2 is a member of the IFI20X /IFI16 family. It plays a putative role in tumorigenic reversion and may control cell proliferation. Interferon-gamma induces expression of AIM2. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2763515).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CADM3	NM_001127173.3	c.59C>G	p.Ala20Gly	missense_variant	Exon 1 of 9	ENST00000368125.9	NP_001120645.1
CADM3	NM_021189.5	c.59C>G	p.Ala20Gly	missense_variant	Exon 1 of 10		NP_067012.1
CADM3	NM_001346510.2	c.59C>G	p.Ala20Gly	missense_variant	Exon 1 of 9		NP_001333439.1
CADM3	XM_024448760.2	c.59C>G	p.Ala20Gly	missense_variant	Exon 1 of 12		XP_024304528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CADM3	ENST00000368125.9	c.59C>G	p.Ala20Gly	missense_variant	Exon 1 of 9	1	NM_001127173.3	ENSP00000357107.4
CADM3	ENST00000368124.8	c.59C>G	p.Ala20Gly	missense_variant	Exon 1 of 10	1		ENSP00000357106.4
CADM3	ENST00000416746.1	c.59C>G	p.Ala20Gly	missense_variant	Exon 1 of 7	1		ENSP00000387802.1
AIM2	ENST00000695582.1	n.33+15987G>C		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Oct 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.59C>G (p.A20G) alteration is located in exon 1 (coding exon 1) of the CADM3 gene. This alteration results from a C to G substitution at nucleotide position 59, causing the alanine (A) at amino acid position 20 to be replaced by a glycine (G). 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	0.074
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	.;T;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.69	T;T;T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.28	T;T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	0.0	N;N;.
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-0.20	N;N;N
REVEL	Benign	0.078
Sift	Pathogenic	0.0	D;T;T
Sift4G	Pathogenic	0.0	D;T;T
Polyphen		0.99	D;D;.
Vest4		0.27
MutPred		0.46		Loss of stability (P = 0.0919);Loss of stability (P = 0.0919);Loss of stability (P = 0.0919);
MVP		0.45
MPC		1.1
ClinPred		0.72	D
GERP RS		3.7
Varity_R		0.12
gMVP		0.18

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-159141614;