rs1044243

Positions:

• chr3-105541676-C-A
• chr3-105541676-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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 Likely benign.

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

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

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
ALCAM	NM_001627.4	c.902C>A	p.Thr301Lys	missense_variant	8/16	ENST00000306107.9	NP_001618.2
ALCAM	NM_001243280.2	c.902C>A	p.Thr301Lys	missense_variant	8/15		NP_001230209.1
ALCAM	NM_001243281.2	c.902C>A	p.Thr301Lys	missense_variant	8/14		NP_001230210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALCAM	ENST00000306107.9	c.902C>A	p.Thr301Lys	missense_variant	8/16	1	NM_001627.4	ENSP00000305988	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 249832 Hom.: 0 AF XY: 0.00000741 AC XY: 1 AN XY: 135016

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 SAS exome AF: 0.00

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 v4.3

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;D;D
M_CAP	Benign	0.0032	T
MetaRNN	Uncertain	0.61	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;L;.
MutationTaster	Benign	0.00052	P;P;P;P
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.69	N;N;N
REVEL	Benign	0.062
Sift	Uncertain	0.015	D;D;D
Sift4G	Uncertain	0.013	D;D;D
Polyphen		0.55	P;.;.
Vest4		0.58
MutPred		0.35		Gain of glycosylation at Y298 (P = 0.0064);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

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: rs1044243; hg19: chr3-105260520;