1-159191945-C-T

Position:

• chr1-159191945-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001127173.3(CADM3):​c.98C>T​(p.Pro33Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CADM3 NM_001127173.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.93

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CADM3	NM_001127173.3	c.98C>T	p.Pro33Leu	missense_variant	2/9	ENST00000368125.9	NP_001120645.1
CADM3	NM_021189.5	c.200C>T	p.Pro67Leu	missense_variant	3/10		NP_067012.1
CADM3	NM_001346510.2	c.98C>T	p.Pro33Leu	missense_variant	2/9		NP_001333439.1
CADM3	XM_024448760.2	c.347C>T	p.Pro116Leu	missense_variant	5/12		XP_024304528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CADM3	ENST00000368125.9	c.98C>T	p.Pro33Leu	missense_variant	2/9	1	NM_001127173.3	ENSP00000357107	P2
CADM3	ENST00000368124.8	c.200C>T	p.Pro67Leu	missense_variant	3/10	1		ENSP00000357106	A2
CADM3	ENST00000416746.1	c.98C>T	p.Pro33Leu	missense_variant	2/7	1		ENSP00000387802

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Feb 27, 2023

The c.200C>T (p.P67L) alteration is located in exon 3 (coding exon 3) of the CADM3 gene. This alteration results from a C to T substitution at nucleotide position 200, causing the proline (P) at amino acid position 67 to be replaced by a leucine (L). 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	0.97
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	.;T;.
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.64	D;D;D
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.3	.;L;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-3.8	D;D;D
REVEL	Benign	0.25
Sift	Uncertain	0.013	D;T;T
Sift4G	Uncertain	0.039	D;T;D
Polyphen		1.0	D;D;.
Vest4		0.84
MutPred		0.44		.;Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);
MVP		0.74
MPC		1.3
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.58
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr1-159161735;