19-10334709-CA-AG

Variant names:

• chr19-10334709-CA-AG
• NM_002162.5:c.1010_1011delTGinsCT
• ICAM3 p.Met337Thr

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PVS1_Supporting

The NM_001395376.1(ICAM3):​c.2_3delTGinsCT​(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ICAM3 NM_001395376.1 start_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.874
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PVS1: Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 141 codons. Genomic position: 10334172. Lost 0.662 part of the original CDS.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395376.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ICAM3	NM_002162.5	MANE Select	c.1010_1011delTGinsCT	p.Met337Thr	missense	N/A	NP_002153.2	P32942
	ICAM3	NM_001395376.1		c.2_3delTGinsCT	p.Met1?	start_lost	N/A	NP_001382305.1	A0A9L9PXS1
	ICAM3	NM_001320606.2		c.779_780delTGinsCT	p.Met260Thr	missense	N/A	NP_001307535.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ICAM3	ENST00000160262.10	TSL:1 MANE Select	c.1010_1011delTGinsCT	p.Met337Thr	missense	N/A	ENSP00000160262.3	P32942
	ICAM3	ENST00000589261.5	TSL:1	n.1312_1313delTGinsCT		non_coding_transcript_exon	Exon 5 of 7
	ICAM3	ENST00000706691.1		c.2_3delTGinsCT	p.Met1?	start_lost	N/A	ENSP00000516505.1	A0A9L9PXS1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.87

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-10445385;