3-105541676-C-T

Position:

• chr3-105541676-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000306107.9(ALCAM):​c.902C>T​(p.Thr301Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,611,820 control chromosomes in the GnomAD database, including 10,505 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.083 (663 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9842 hom.)
• Consequence: ALCAM ENST00000306107.9 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0027675033).
• BP6: Variant 3-105541676-C-T is Benign according to our data. Variant chr3-105541676-C-T is described in ClinVar as [Benign]. Clinvar id is 1242703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALCAM	NM_001627.4	c.902C>T	p.Thr301Met	missense_variant	8/16	ENST00000306107.9	NP_001618.2
ALCAM	NM_001243280.2	c.902C>T	p.Thr301Met	missense_variant	8/15		NP_001230209.1
ALCAM	NM_001243281.2	c.902C>T	p.Thr301Met	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>T	p.Thr301Met	missense_variant	8/16	1	NM_001627.4	ENSP00000305988	A1

Frequencies

GnomAD3 genomes AF: 0.0833 AC: 12640 AN: 151756 Hom.: 665 Cov.: 32

Gnomad AFR AF: 0.0260

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.0661

Gnomad ASJ AF: 0.0758

Gnomad EAS AF: 0.0401

Gnomad SAS AF: 0.0629

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.0718

GnomAD3 exomes AF: 0.0875 AC: 21871 AN: 249832 Hom.: 1164 AF XY: 0.0889 AC XY: 12009 AN XY: 135016

Gnomad AFR exome AF: 0.0232

Gnomad AMR exome AF: 0.0468

Gnomad ASJ exome AF: 0.0765

Gnomad EAS exome AF: 0.0433

Gnomad SAS exome AF: 0.0624

Gnomad FIN exome AF: 0.115

Gnomad NFE exome AF: 0.119

Gnomad OTH exome AF: 0.0920

GnomAD4 exome AF: 0.111 AC: 161863 AN: 1459946 Hom.: 9842 Cov.: 35 AF XY: 0.110 AC XY: 79867 AN XY: 726268

Gnomad4 AFR exome AF: 0.0202

Gnomad4 AMR exome AF: 0.0488

Gnomad4 ASJ exome AF: 0.0781

Gnomad4 EAS exome AF: 0.0359

Gnomad4 SAS exome AF: 0.0619

Gnomad4 FIN exome AF: 0.119

Gnomad4 NFE exome AF: 0.124

Gnomad4 OTH exome AF: 0.0994

GnomAD4 genome AF: 0.0832 AC: 12631 AN: 151874 Hom.: 663 Cov.: 32 AF XY: 0.0823 AC XY: 6107 AN XY: 74228

Gnomad4 AFR AF: 0.0259

Gnomad4 AMR AF: 0.0659

Gnomad4 ASJ AF: 0.0758

Gnomad4 EAS AF: 0.0404

Gnomad4 SAS AF: 0.0625

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.0710

Alfa AF: 0.100 Hom.: 454

Bravo AF: 0.0759

TwinsUK AF: 0.117 AC: 435

ALSPAC AF: 0.117 AC: 451

ESP6500AA AF: 0.0284 AC: 125

ESP6500EA AF: 0.118 AC: 1012

ExAC AF: 0.0888 AC: 10783

Asia WGS AF: 0.0410 AC: 143 AN: 3478

EpiCase AF: 0.113

EpiControl AF: 0.114

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 17, 2020	This variant is associated with the following publications: (PMID: 21935604) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.59
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T;.;.
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.78	T;T;T
MetaRNN	Benign	0.0028	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;M;.
MutationTaster	Benign	0.00094	P;P;P;P
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-2.1	N;N;N
REVEL	Benign	0.10
Sift	Uncertain	0.027	D;D;D
Sift4G	Benign	0.14	T;T;T
Polyphen		0.20	B;.;.
Vest4		0.14
MPC		0.41
ClinPred		0.0086	T
GERP RS		5.3
Varity_R		0.080
gMVP		0.54

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; COSMIC: COSV60246405; COSMIC: COSV60246405;