11-115209588-A-G

Variant names:

• chr11-115209588-A-G
• NM_001301043.2:c.1064T>C

Variant summary

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

The NM_001301043.2(CADM1):​c.1064T>C​(p.Leu355Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CADM1 NM_001301043.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.05

Genes affected

CADM1 (HGNC:5951): (cell adhesion molecule 1) Enables signaling receptor binding activity. Involved in several processes, including cell recognition; positive regulation of cytokine production; and susceptibility to natural killer cell mediated cytotoxicity. Located in plasma membrane. Implicated in breast carcinoma and prostate cancer. Biomarker of cervix uteri carcinoma in situ. [provided by Alliance of Genome Resources, Apr 2022]

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 rank	MANE	Protein	UniProt
CADM1	NM_001301043.2	c.1064T>C	p.Leu355Pro	missense_variant	Exon 8 of 12	ENST00000331581.11	NP_001287972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CADM1	ENST00000331581.11	c.1064T>C	p.Leu355Pro	missense_variant	Exon 8 of 12	1	NM_001301043.2	ENSP00000329797.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1064T>C (p.L355P) alteration is located in exon 8 (coding exon 8) of the CADM1 gene. This alteration results from a T to C substitution at nucleotide position 1064, causing the leucine (L) at amino acid position 355 to be replaced by a proline (P). 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	0.12
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	18
DANN	Benign	0.86
DEOGEN2	Benign	0.026	T;.;.;T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.60	T;T;T;T
M_CAP	Benign	0.0084	T
MetaRNN	Uncertain	0.52	D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N;N;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	0.0	N;N;N;.
REVEL	Benign	0.15
Sift	Benign	0.36	T;T;T;.
Sift4G	Benign	0.33	T;T;T;T
Polyphen		0.0	B;.;.;.
Vest4		0.39
MutPred		0.88		Gain of disorder (P = 0.0048);Gain of disorder (P = 0.0048);Gain of disorder (P = 0.0048);.;
MVP		0.58
MPC		1.0
ClinPred		0.20	T
GERP RS		1.1
Varity_R		0.16
gMVP		0.83

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: chr11-115080308;