3-105545332-G-T

Variant names:

• chr3-105545332-G-T
• rs34926152
• NM_001627.4:c.1101G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001627.4(ALCAM):​c.1101G>T​(p.Met367Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0422 in 1,602,180 control chromosomes in the GnomAD database, including 1,619 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.033 (122 hom., cov: 32)
  • Exomes 𝑓: 0.043 (1497 hom.)
• Consequence: ALCAM NM_001627.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44
• Publications: 14 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00520584).
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALCAM	NM_001627.4	c.1101G>T	p.Met367Ile	missense_variant	Exon 9 of 16	ENST00000306107.9	NP_001618.2
ALCAM	NM_001243280.2	c.1101G>T	p.Met367Ile	missense_variant	Exon 9 of 15		NP_001230209.1
ALCAM	NM_001243281.2	c.1101G>T	p.Met367Ile	missense_variant	Exon 9 of 14		NP_001230210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALCAM	ENST00000306107.9	c.1101G>T	p.Met367Ile	missense_variant	Exon 9 of 16	1	NM_001627.4	ENSP00000305988.5

Frequencies

GnomAD3 genomes AF: 0.0326 AC: 4943 AN: 151462 Hom.: 122 Cov.: 32

Gnomad AFR AF: 0.00914

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0306

Gnomad ASJ AF: 0.0769

Gnomad EAS AF: 0.000388

Gnomad SAS AF: 0.0189

Gnomad FIN AF: 0.0349

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0481

Gnomad OTH AF: 0.0331

GnomAD2 exomes AF: 0.0346 AC: 8656 AN: 249926 AF XY: 0.0356

Gnomad AFR exome AF: 0.00829

Gnomad AMR exome AF: 0.0215

Gnomad ASJ exome AF: 0.0828

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0368

Gnomad NFE exome AF: 0.0471

Gnomad OTH exome AF: 0.0390

GnomAD4 exome AF: 0.0432 AC: 62677 AN: 1450600 Hom.: 1497 Cov.: 29 AF XY: 0.0426 AC XY: 30771 AN XY: 722188

African (AFR) AF: 0.00768 AC: 254 AN: 33052

American (AMR) AF: 0.0227 AC: 1008 AN: 44500

Ashkenazi Jewish (ASJ) AF: 0.0823 AC: 2126 AN: 25832

East Asian (EAS) AF: 0.0000759 AC: 3 AN: 39520

South Asian (SAS) AF: 0.0208 AC: 1787 AN: 86008

European-Finnish (FIN) AF: 0.0364 AC: 1940 AN: 53264

Middle Eastern (MID) AF: 0.0583 AC: 333 AN: 5716

European-Non Finnish (NFE) AF: 0.0478 AC: 52730 AN: 1102912

Other (OTH) AF: 0.0417 AC: 2496 AN: 59796

GnomAD4 genome AF: 0.0326 AC: 4942 AN: 151580 Hom.: 122 Cov.: 32 AF XY: 0.0315 AC XY: 2333 AN XY: 74088

African (AFR) AF: 0.00911 AC: 378 AN: 41476

American (AMR) AF: 0.0306 AC: 464 AN: 15160

Ashkenazi Jewish (ASJ) AF: 0.0769 AC: 265 AN: 3448

East Asian (EAS) AF: 0.000389 AC: 2 AN: 5146

South Asian (SAS) AF: 0.0189 AC: 91 AN: 4822

European-Finnish (FIN) AF: 0.0349 AC: 371 AN: 10618

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0481 AC: 3252 AN: 67598

Other (OTH) AF: 0.0328 AC: 69 AN: 2106

Alfa AF: 0.0415 Hom.: 291

Bravo AF: 0.0303

TwinsUK AF: 0.0502 AC: 186

ALSPAC AF: 0.0542 AC: 209

ESP6500AA AF: 0.00953 AC: 42

ESP6500EA AF: 0.0502 AC: 432

ExAC AF: 0.0337 AC: 4096

Asia WGS AF: 0.0120 AC: 44 AN: 3478

EpiCase AF: 0.0483

EpiControl AF: 0.0565

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.14	T;.;.
Eigen	Benign	-0.17
Eigen_PC	Benign	0.037
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.85	T;T;T
MetaRNN	Benign	0.0052	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.90	L;L;.
PhyloP100		1.4
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.62	N;N;N
REVEL	Benign	0.063
Sift	Benign	0.48	T;T;T
Sift4G	Benign	0.54	T;T;T
Vest4		0.068
ClinPred		0.0065	T
GERP RS		5.3
Varity_R		0.071
gMVP		0.43
Mutation Taster		=95/5	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs34926152; hg19: chr3-105264176; COSMIC: COSV107380065; COSMIC: COSV107380065;