NM_001301043.2:c.898A>C

Variant names:

• chr11-115214704-T-G
• rs374153035
• NM_001301043.2:c.898A>C

Variant summary

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

The NM_001301043.2(CADM1):​c.898A>C​(p.Ile300Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,176 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: CADM1 NM_001301043.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.78

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.898A>C	p.Ile300Leu	missense_variant	Exon 7 of 12	ENST00000331581.11	NP_001287972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CADM1	ENST00000331581.11	c.898A>C	p.Ile300Leu	missense_variant	Exon 7 of 12	1	NM_001301043.2	ENSP00000329797.6

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152176 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152176 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74342

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.099	T;.;.;.;T;.;T
Eigen	Benign	0.062
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.88	D;D;D;D;D;D;D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.62	D;D;D;D;D;D;D
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.2	L;.;L;L;.;L;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.83	N;.;N;N;N;N;.
REVEL	Uncertain	0.35
Sift	Benign	0.28	T;.;T;T;T;T;.
Sift4G	Uncertain	0.027	D;D;D;D;D;D;D
Polyphen		0.014	B;.;.;.;.;.;.
Vest4		0.77
MutPred		0.62		Gain of ubiquitination at K305 (P = 0.071);.;Gain of ubiquitination at K305 (P = 0.071);Gain of ubiquitination at K305 (P = 0.071);Gain of ubiquitination at K305 (P = 0.071);Gain of ubiquitination at K305 (P = 0.071);.;
MVP		0.83
MPC		0.86
ClinPred		0.85	D
GERP RS		5.6
Varity_R		0.39
gMVP		0.68

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

LitVar

Other links and lift over

dbSNP: rs374153035; hg19: chr11-115085424;