chr19-10333883-C-T

Variant names:

• chr19-10333883-C-T
• rs1246125087
• NM_002162.5:c.1618G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002162.5(ICAM3):​c.1618G>A​(p.Gly540Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ICAM3 NM_002162.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.542

Genes affected

ICAM3 (HGNC:5346): (intercellular adhesion molecule 3) The protein encoded by this gene is a member of the intercellular adhesion molecule (ICAM) family. All ICAM proteins are type I transmembrane glycoproteins, contain 2-9 immunoglobulin-like C2-type domains, and bind to the leukocyte adhesion LFA-1 protein. This protein is constitutively and abundantly expressed by all leucocytes and may be the most important ligand for LFA-1 in the initiation of the immune response. It functions not only as an adhesion molecule, but also as a potent signalling molecule. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2016]

ENSG00000274425 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.070647895).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ICAM3	NM_002162.5	c.1618G>A	p.Gly540Arg	missense_variant	Exon 7 of 7	ENST00000160262.10	NP_002153.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ICAM3	ENST00000160262.10	c.1618G>A	p.Gly540Arg	missense_variant	Exon 7 of 7	1	NM_002162.5	ENSP00000160262.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	7.8
DANN	Benign	0.85
DEOGEN2	Benign	0.074	T;T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.095	N
LIST_S2	Benign	0.47	T;T;T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.071	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.55	N;.;.
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-2.8	D;.;.
REVEL	Benign	0.092
Sift	Uncertain	0.014	D;.;.
Sift4G	Benign	0.20	T;T;T
Polyphen		0.0080	B;.;.
Vest4		0.14
MutPred		0.059		Gain of solvent accessibility (P = 0.0456);.;.;
MVP		0.22
MPC		0.51
ClinPred		0.068	T
GERP RS		2.3
Varity_R		0.11
gMVP		0.26

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: rs1246125087; hg19: chr19-10444559; COSMIC: COSV105030829; COSMIC: COSV105030829;