3-105541676-C-A

Variant names:

• chr3-105541676-C-A
• rs1044243
• NM_001627.4:c.902C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001627.4(ALCAM):​c.902C>A​(p.Thr301Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T301M) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ALCAM NM_001627.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.86
• Publications: 25 publications found

Genes affected

ALCAM (HGNC:400): (activated leukocyte cell adhesion molecule) This gene encodes activated leukocyte cell adhesion molecule (ALCAM), also known as CD166 (cluster of differentiation 166), which is a member of a subfamily of immunoglobulin receptors with five immunoglobulin-like domains (VVC2C2C2) in the extracellular domain. This protein binds to T-cell differentiation antigene CD6, and is implicated in the processes of cell adhesion and migration. Multiple alternatively spliced transcript variants encoding different isoforms have been found. [provided by RefSeq, Aug 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001627.4. 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
	ALCAM	NM_001627.4	MANE Select	c.902C>A	p.Thr301Lys	missense	Exon 8 of 16	NP_001618.2	Q13740-1
	ALCAM	NM_001243280.2		c.902C>A	p.Thr301Lys	missense	Exon 8 of 15	NP_001230209.1	Q13740-2
	ALCAM	NM_001243281.2		c.902C>A	p.Thr301Lys	missense	Exon 8 of 14	NP_001230210.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALCAM	ENST00000306107.9	TSL:1 MANE Select	c.902C>A	p.Thr301Lys	missense	Exon 8 of 16	ENSP00000305988.5	Q13740-1
	ALCAM	ENST00000472644.6	TSL:1	c.902C>A	p.Thr301Lys	missense	Exon 8 of 15	ENSP00000419236.2	Q13740-2
	ALCAM	ENST00000880066.1		c.968C>A	p.Thr323Lys	missense	Exon 8 of 16	ENSP00000550125.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 249832 AF XY: 0.00000741

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.090	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0032	T
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		2.9
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.062
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.013	D
Polyphen		0.55	P
Vest4		0.58
MutPred		0.35		Gain of glycosylation at Y298 (P = 0.0064)
MVP		0.25
MPC		0.33
ClinPred		0.84	D
GERP RS		5.3
Varity_R		0.17
gMVP		0.69
Mutation Taster		=82/18	polymorphism

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

Other links and lift over

dbSNP: rs1044243; hg19: chr3-105260520;