3-105524357-C-T

Variant names:

• chr3-105524357-C-T
• rs147777853
• NM_001627.4:c.243C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_001627.4(ALCAM):​c.243C>T​(p.Asp81Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000489 in 1,614,008 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0025 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00028 (3 hom.)
• Consequence: ALCAM NM_001627.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.19
• Publications: 2 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 3-105524357-C-T is Benign according to our data. Variant chr3-105524357-C-T is described in ClinVar as [Benign]. Clinvar id is 711883.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.19 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALCAM	NM_001627.4	c.243C>T	p.Asp81Asp	synonymous_variant	Exon 3 of 16	ENST00000306107.9	NP_001618.2
ALCAM	NM_001243280.2	c.243C>T	p.Asp81Asp	synonymous_variant	Exon 3 of 15		NP_001230209.1
ALCAM	NM_001243281.2	c.243C>T	p.Asp81Asp	synonymous_variant	Exon 3 of 14		NP_001230210.1
ALCAM	NM_001243283.2	c.243C>T	p.Asp81Asp	synonymous_variant	Exon 3 of 3		NP_001230212.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALCAM	ENST00000306107.9	c.243C>T	p.Asp81Asp	synonymous_variant	Exon 3 of 16	1	NM_001627.4	ENSP00000305988.5

Frequencies

GnomAD3 genomes AF: 0.00249 AC: 378 AN: 152062 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00881

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.000585 AC: 147 AN: 251442 AF XY: 0.000434

Gnomad AFR exome AF: 0.00775

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000280 AC: 409 AN: 1461830 Hom.: 3 Cov.: 31 AF XY: 0.000250 AC XY: 182 AN XY: 727212

African (AFR) AF: 0.00968 AC: 324 AN: 33480

American (AMR) AF: 0.000291 AC: 13 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39692

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.0000171 AC: 19 AN: 1111970

Other (OTH) AF: 0.000662 AC: 40 AN: 60392

GnomAD4 genome AF: 0.00250 AC: 380 AN: 152178 Hom.: 1 Cov.: 32 AF XY: 0.00232 AC XY: 173 AN XY: 74416

African (AFR) AF: 0.00884 AC: 367 AN: 41536

American (AMR) AF: 0.000262 AC: 4 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67960

Other (OTH) AF: 0.00284 AC: 6 AN: 2112

Alfa AF: 0.00125 Hom.: 0

Bravo AF: 0.00275

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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

- -

May 21, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	6.6
DANN	Benign	0.55
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism

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: rs147777853; hg19: chr3-105243201;