3-105524499-A-C

Position:

• chr3-105524499-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000306107.9(ALCAM):​c.385A>C​(p.Lys129Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ALCAM ENST00000306107.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.58

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3851142).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALCAM	NM_001627.4	c.385A>C	p.Lys129Gln	missense_variant	3/16	ENST00000306107.9	NP_001618.2
ALCAM	NM_001243280.2	c.385A>C	p.Lys129Gln	missense_variant	3/15		NP_001230209.1
ALCAM	NM_001243281.2	c.385A>C	p.Lys129Gln	missense_variant	3/14		NP_001230210.1
ALCAM	NM_001243283.2	c.385A>C	p.Lys129Gln	missense_variant	3/3		NP_001230212.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALCAM	ENST00000306107.9	c.385A>C	p.Lys129Gln	missense_variant	3/16	1	NM_001627.4	ENSP00000305988	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 16, 2023

The c.385A>C (p.K129Q) alteration is located in exon 3 (coding exon 3) of the ALCAM gene. This alteration results from a A to C substitution at nucleotide position 385, causing the lysine (K) at amino acid position 129 to be replaced by a glutamine (Q). 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	0.19
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T;.;.
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.39	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M;M;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.3	N;N;N
REVEL	Benign	0.091
Sift	Benign	0.21	T;T;T
Sift4G	Uncertain	0.021	D;D;D
Polyphen		0.86	P;.;.
Vest4		0.56
MutPred		0.48		Loss of methylation at K129 (P = 0.0041);Loss of methylation at K129 (P = 0.0041);.;
MVP		0.50
MPC		0.40
ClinPred		0.71	D
GERP RS		5.9
Varity_R		0.23
gMVP		0.64

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: chr3-105243343;