3-105541676-C-T

Variant names:

• chr3-105541676-C-T
• rs1044243
• NM_001627.4:c.902C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001627.4(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 (★★).

• Frequency:
  • Genomes: 𝑓 0.083 (663 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9842 hom.)
• Consequence: ALCAM NM_001627.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.86
• Publications: 25 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: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
ALCAM	NM_001627.4	c.902C>T	p.Thr301Met	missense_variant	Exon 8 of 16	ENST00000306107.9	NP_001618.2
ALCAM	NM_001243280.2	c.902C>T	p.Thr301Met	missense_variant	Exon 8 of 15		NP_001230209.1
ALCAM	NM_001243281.2	c.902C>T	p.Thr301Met	missense_variant	Exon 8 of 14		NP_001230210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALCAM	ENST00000306107.9	c.902C>T	p.Thr301Met	missense_variant	Exon 8 of 16	1	NM_001627.4	ENSP00000305988.5

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

GnomAD2 exomes AF: 0.0875 AC: 21871 AN: 249832 AF XY: 0.0889

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 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

African (AFR) AF: 0.0202 AC: 673 AN: 33354

American (AMR) AF: 0.0488 AC: 2177 AN: 44604

Ashkenazi Jewish (ASJ) AF: 0.0781 AC: 2034 AN: 26056

East Asian (EAS) AF: 0.0359 AC: 1422 AN: 39664

South Asian (SAS) AF: 0.0619 AC: 5338 AN: 86178

European-Finnish (FIN) AF: 0.119 AC: 6336 AN: 53356

Middle Eastern (MID) AF: 0.0806 AC: 464 AN: 5754

European-Non Finnish (NFE) AF: 0.124 AC: 137425 AN: 1110700

Other (OTH) AF: 0.0994 AC: 5994 AN: 60280

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

African (AFR) AF: 0.0259 AC: 1073 AN: 41482

American (AMR) AF: 0.0659 AC: 1003 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.0758 AC: 263 AN: 3468

East Asian (EAS) AF: 0.0404 AC: 208 AN: 5144

South Asian (SAS) AF: 0.0625 AC: 302 AN: 4832

European-Finnish (FIN) AF: 0.115 AC: 1215 AN: 10568

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8274 AN: 67850

Other (OTH) AF: 0.0710 AC: 150 AN: 2112

Alfa AF: 0.101 Hom.: 593

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 17, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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;.
PhyloP100		2.9
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
Mutation Taster		=94/6	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1044243; hg19: chr3-105260520; COSMIC: COSV60246405; COSMIC: COSV60246405;