19-10334288-T-G

Position:

• chr19-10334288-T-G

Variant summary

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

The NM_002162.5(ICAM3):​c.1313A>C​(p.Glu438Ala) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ICAM3 NM_002162.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.657

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]

(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=0.120690346).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ICAM3	NM_002162.5	c.1313A>C	p.Glu438Ala	missense_variant	6/7	ENST00000160262.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ICAM3	ENST00000160262.10	c.1313A>C	p.Glu438Ala	missense_variant	6/7	1	NM_002162.5	P1
	ENST00000612689.1	n.853T>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.082	T;T;T;T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.49	T;T;T;T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.12	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.3	M;.;.;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.8	D;.;.;.
REVEL	Benign	0.051
Sift	Benign	0.13	T;.;.;.
Sift4G	Benign	0.22	T;T;T;.
Polyphen		0.47	P;.;.;.
Vest4		0.14
MutPred		0.33		Loss of ubiquitination at K437 (P = 0.0382);.;.;.;
MVP		0.39
MPC		0.96
ClinPred		0.68	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.14
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1599309534; hg19: chr19-10444964;