rs76635565

Variant names:

• chr3-105533637-A-G
• rs76635565
• NM_001627.4:c.494A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-105533637-A-G
• chr3-105533637-A-T

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.494A>G​(p.Asp165Gly) 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. 16/22 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. D165V) 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: 2.15
• 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=0.24378061).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALCAM	NM_001627.4	c.494A>G	p.Asp165Gly	missense_variant	Exon 5 of 16	ENST00000306107.9	NP_001618.2
ALCAM	NM_001243280.2	c.494A>G	p.Asp165Gly	missense_variant	Exon 5 of 15		NP_001230209.1
ALCAM	NM_001243281.2	c.494A>G	p.Asp165Gly	missense_variant	Exon 5 of 14		NP_001230210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALCAM	ENST00000306107.9	c.494A>G	p.Asp165Gly	missense_variant	Exon 5 of 16	1	NM_001627.4	ENSP00000305988.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251184 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

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	0.14
BayesDel_addAF	Benign	-0.0027	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.32	T;.;.
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	1.6	L;L;.
PhyloP100		2.1
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.75	N;N;N
REVEL	Benign	0.18
Sift	Benign	0.089	T;T;T
Sift4G	Uncertain	0.045	D;D;D
Polyphen		0.32	B;.;.
Vest4		0.34
MutPred		0.60		Gain of glycosylation at Y163 (P = 0.0131);Gain of glycosylation at Y163 (P = 0.0131);.;
MVP		0.77
MPC		0.29
ClinPred		0.14	T
GERP RS		1.9
PromoterAI		-0.00030	Neutral
Varity_R		0.27
gMVP		0.66
Mutation Taster		=61/39	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs76635565; hg19: chr3-105252481;