chr1-159191945-C-T

Variant names:

• chr1-159191945-C-T
• NM_001127173.3:c.98C>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP2

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
• Publications: 0 publications found

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]

CADM3-AS1 (HGNC:40812): (CADM3 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 1 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 1.6917 (below the threshold of 3.09). Trascript score misZ: 1.5575 (below the threshold of 3.09). GenCC associations: The gene is linked to Charcot-Marie-Tooth disease, axonal, type 2FF.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127173.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CADM3	NM_001127173.3	MANE Select	c.98C>T	p.Pro33Leu	missense	Exon 2 of 9	NP_001120645.1	Q8N126-1
	CADM3	NM_021189.5		c.200C>T	p.Pro67Leu	missense	Exon 3 of 10	NP_067012.1	Q8N126-2
	CADM3	NM_001346510.2		c.98C>T	p.Pro33Leu	missense	Exon 2 of 9	NP_001333439.1	Q8N126-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CADM3	ENST00000368125.9	TSL:1 MANE Select	c.98C>T	p.Pro33Leu	missense	Exon 2 of 9	ENSP00000357107.4	Q8N126-1
	CADM3	ENST00000368124.8	TSL:1	c.200C>T	p.Pro67Leu	missense	Exon 3 of 10	ENSP00000357106.4	Q8N126-2
	CADM3	ENST00000416746.1	TSL:1	c.98C>T	p.Pro33Leu	missense	Exon 2 of 7	ENSP00000387802.1	A0A0C4DG09

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.3	L
PhyloP100		6.9
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.25
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.039	D
Polyphen		1.0	D
Vest4		0.84
MutPred		0.44		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
Mutation Taster		=43/57	disease causing

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

Other links and lift over

hg19: chr1-159161735;