chr19-10335892-T-G

Position:

• chr19-10335892-T-G

Variant summary

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

The ENST00000160262.10(ICAM3):​c.428A>C​(p.Asp143Ala) 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. 15/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. D143G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ICAM3 ENST00000160262.10 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.621

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=0.120132476).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ICAM3	NM_002162.5	c.428A>C	p.Asp143Ala	missense_variant	3/7	ENST00000160262.10	NP_002153.2
ICAM3	NM_001320606.2	c.197A>C	p.Asp66Ala	missense_variant	3/7		NP_001307535.1
ICAM3	NM_001320605.2	c.428A>C	p.Asp143Ala	missense_variant	3/6		NP_001307534.1
ICAM3	NM_001320608.2	c.-673A>C		5_prime_UTR_variant	3/6		NP_001307537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ICAM3	ENST00000160262.10	c.428A>C	p.Asp143Ala	missense_variant	3/7	1	NM_002162.5	ENSP00000160262	P1
	ENST00000612689.1	n.2457T>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.061	T;T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.48	T;T;T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.060	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.3	N;.;.
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.91	N;.;.
REVEL	Benign	0.12
Sift	Uncertain	0.0010	D;.;.
Sift4G	Uncertain	0.0060	D;D;.
Polyphen		0.0010	B;.;.
Vest4		0.15
MutPred		0.27		Gain of sheet (P = 0.0827);.;.;
MVP		0.12
MPC		0.50
ClinPred		0.55	D
GERP RS		5.0
Varity_R		0.074
gMVP		0.70

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: rs2304237; hg19: chr19-10446568;