chr1-159193507-G-A

Position:

• chr1-159193507-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_Moderate BS2

The NM_001127173.3(CADM3):​c.467G>A​(p.Gly156Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: CADM3 NM_001127173.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.66

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.874
• BS2: High AC in GnomAdExome4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CADM3	NM_001127173.3	c.467G>A	p.Gly156Glu	missense_variant	4/9	ENST00000368125.9	NP_001120645.1
CADM3	NM_021189.5	c.569G>A	p.Gly190Glu	missense_variant	5/10		NP_067012.1
CADM3	NM_001346510.2	c.467G>A	p.Gly156Glu	missense_variant	4/9		NP_001333439.1
CADM3	XM_024448760.2	c.716G>A	p.Gly239Glu	missense_variant	7/12		XP_024304528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CADM3	ENST00000368125.9	c.467G>A	p.Gly156Glu	missense_variant	4/9	1	NM_001127173.3	ENSP00000357107	P2
CADM3	ENST00000368124.8	c.569G>A	p.Gly190Glu	missense_variant	5/10	1		ENSP00000357106	A2
CADM3	ENST00000416746.1	c.467G>A	p.Gly156Glu	missense_variant	4/7	1		ENSP00000387802

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000109 AC: 16 AN: 1461858 Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8 AN XY: 727222

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000135

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 06, 2023

The c.569G>A (p.G190E) alteration is located in exon 5 (coding exon 5) of the CADM3 gene. This alteration results from a G to A substitution at nucleotide position 569, causing the glycine (G) at amino acid position 190 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	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.44	D
BayesDel_noAF	Pathogenic	0.40
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.66	.;D;.
Eigen	Pathogenic	0.91
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Uncertain	0.19	D
MetaRNN	Pathogenic	0.87	D;D;D
MetaSVM	Uncertain	0.77	D
MutationAssessor	Uncertain	2.7	.;M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-4.3	D;D;D
REVEL	Pathogenic	0.79
Sift	Uncertain	0.010	D;D;D
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.83
MutPred		0.65		.;Loss of MoRF binding (P = 0.0308);Loss of MoRF binding (P = 0.0308);
MVP		0.94
MPC		1.4
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.65
gMVP		0.91

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: chr1-159163297;