3-105534771-C-G

Position:

• chr3-105534771-C-G

Variant summary

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

The NM_001627.4(ALCAM):​c.656C>G​(p.Thr219Ser) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ALCAM NM_001627.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.71

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=0.36438644).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALCAM	NM_001627.4	c.656C>G	p.Thr219Ser	missense_variant	6/16	ENST00000306107.9
ALCAM	NM_001243280.2	c.656C>G	p.Thr219Ser	missense_variant	6/15
ALCAM	NM_001243281.2	c.656C>G	p.Thr219Ser	missense_variant	6/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALCAM	ENST00000306107.9	c.656C>G	p.Thr219Ser	missense_variant	6/16	1	NM_001627.4	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000546

EpiControl AF: 0.00

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

Jul 13, 2021

The c.656C>G (p.T219S) alteration is located in exon 6 (coding exon 6) of the ALCAM gene. This alteration results from a C to G substitution at nucleotide position 656, causing the threonine (T) at amino acid position 219 to be replaced by a serine (S). 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	0.077
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.24	T;.;.
Eigen	Benign	-0.18
Eigen_PC	Benign	0.053
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.70	T;T;T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.36	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.1	L;L;.
MutationTaster	Benign	0.97	D;D;D;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.19	N;N;N
REVEL	Benign	0.083
Sift	Benign	0.28	T;T;T
Sift4G	Benign	0.60	T;T;T
Polyphen		0.022	B;.;.
Vest4		0.20
MutPred		0.69		Gain of glycosylation at Y224 (P = 0.0525);Gain of glycosylation at Y224 (P = 0.0525);.;
MVP		0.37
MPC		0.25
ClinPred		0.77	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.23
gMVP		0.40

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: chr3-105253615;