chr3-105524360-T-G

Variant names:

• chr3-105524360-T-G
• rs150607806
• NM_001627.4:c.246T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001627.4(ALCAM):​c.246T>G​(p.Asp82Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 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. D82N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ALCAM NM_001627.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.454
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11233804).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALCAM	NM_001627.4	c.246T>G	p.Asp82Glu	missense_variant	Exon 3 of 16	ENST00000306107.9	NP_001618.2
ALCAM	NM_001243280.2	c.246T>G	p.Asp82Glu	missense_variant	Exon 3 of 15		NP_001230209.1
ALCAM	NM_001243281.2	c.246T>G	p.Asp82Glu	missense_variant	Exon 3 of 14		NP_001230210.1
ALCAM	NM_001243283.2	c.246T>G	p.Asp82Glu	missense_variant	Exon 3 of 3		NP_001230212.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALCAM	ENST00000306107.9	c.246T>G	p.Asp82Glu	missense_variant	Exon 3 of 16	1	NM_001627.4	ENSP00000305988.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	16
DANN	Benign	0.95
DEOGEN2	Benign	0.10	T;.;.
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.82
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.81	T;T;T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;L;.
PhyloP100		0.45
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	0.34	N;N;N
REVEL	Benign	0.048
Sift	Benign	0.26	T;T;T
Sift4G	Benign	0.75	T;T;T
Polyphen		0.0030	B;.;.
Vest4		0.31
MutPred		0.45		Gain of glycosylation at Y80 (P = 0.0014);Gain of glycosylation at Y80 (P = 0.0014);.;
MVP		0.42
MPC		0.19
ClinPred		0.11	T
GERP RS		-2.1
Varity_R		0.16
gMVP		0.67
Mutation Taster		=74/26	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs150607806; hg19: chr3-105243204;