Variant 3-105545332-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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. 13/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.033 ( 122 hom., cov: 32)

Exomes 𝑓: 0.043 ( 1497 hom. )

Consequence

ALCAM
NM_001627.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.44

Variant links:

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]

ALCAM links:

ALCAM (HGNC:):

ALCAM links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ALCAM	NM_001627.4 linkuse as main transcript	c.1101G>T	p.Met367Ile	missense_variant	9/16	ENST00000306107.9	NP_001618.2	Q13740-1
ALCAM	NM_001243280.2 linkuse as main transcript	c.1101G>T	p.Met367Ile	missense_variant	9/15		NP_001230209.1	Q13740-2
ALCAM	NM_001243281.2 linkuse as main transcript	c.1101G>T	p.Met367Ile	missense_variant	9/14		NP_001230210.1	B3KNN9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALCAM	ENST00000306107.9 linkuse as main transcript	c.1101G>T	p.Met367Ile	missense_variant	9/16	1	NM_001627.4	ENSP00000305988.5		Q13740-1

Frequencies

GnomAD3 genomes

AF:

0.0326

AC:

4943

AN:

151462

Hom.:

122

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0346

AC:

8656

AN:

249926

Hom.:

195

AF XY:

0.0356

AC XY:

4810

AN XY:

135082

show subpopulations

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 SAS exome

AF:

0.0201

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.:

AF XY:

0.0426

AC XY:

30771

AN XY:

722188

show subpopulations

Gnomad4 AFR exome

AF:

0.00768

Gnomad4 AMR exome

AF:

0.0227

Gnomad4 ASJ exome

AF:

0.0823

Gnomad4 EAS exome

AF:

0.0000759

Gnomad4 SAS exome

AF:

0.0208

Gnomad4 FIN exome

AF:

0.0364

Gnomad4 NFE exome

AF:

0.0478

Gnomad4 OTH exome

AF:

0.0417

GnomAD4 genome

AF:

0.0326

AC:

4942

AN:

151580

Hom.:

122

Cov.:

AF XY:

0.0315

AC XY:

2333

AN XY:

74088

show subpopulations

Gnomad4 AFR

AF:

0.00911

Gnomad4 AMR

AF:

0.0306

Gnomad4 ASJ

AF:

0.0769

Gnomad4 EAS

AF:

0.000389

Gnomad4 SAS

AF:

0.0189

Gnomad4 FIN

AF:

0.0349

Gnomad4 NFE

AF:

0.0481

Gnomad4 OTH

AF:

0.0328

Alfa

AF:

0.0444

Hom.:

231

Bravo

AF:

0.0303

TwinsUK

AF:

0.0502

AC:

186

ALSPAC

AF:

0.0542

AC:

209

ESP6500AA

AF:

0.00953

AC:

ESP6500EA

AF:

0.0502

AC:

432

ExAC

AF:

0.0337

AC:

4096

Asia WGS

AF:

0.0120

AC:

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

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.14

T;.;.

Eigen

Benign

-0.17

Eigen_PC

Benign

0.037

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.85

T;T;T

MetaRNN

Benign

0.0052

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.90

L;L;.

PrimateAI

Uncertain

0.53

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

Polyphen

0.0010

B;.;.

Vest4

0.068

MutPred

0.21

Gain of methylation at K368 (P = 0.0227);Gain of methylation at K368 (P = 0.0227);.;

MPC

0.23

ClinPred

0.0065

GERP RS

5.3

Varity_R

0.071

gMVP

0.43

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over