19-54360050-GG-AA

Variant names:

• chr19-54360050-GG-AA
• NM_002287.6:c.386_387delCCinsTT
• LAIR1 p.Ser129Phe

Variant summary

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

The NM_002287.6(LAIR1):​c.386_387delCCinsTT​(p.Ser129Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 15)
• Consequence: LAIR1 NM_002287.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.847
• Publications: 0 publications found

Genes affected

LAIR1 (HGNC:6477): (leukocyte associated immunoglobulin like receptor 1) The protein encoded by this gene is an inhibitory receptor found on peripheral mononuclear cells, including natural killer cells, T cells, and B cells. Inhibitory receptors regulate the immune response to prevent lysis of cells recognized as self. The gene is a member of both the immunoglobulin superfamily and the leukocyte-associated inhibitory receptor family. The gene maps to a region of 19q13.4 called the leukocyte receptor cluster, which contains at least 29 genes encoding leukocyte-expressed receptors of the immunoglobulin superfamily. The encoded protein has been identified as an anchor for tyrosine phosphatase SHP-1, and may induce cell death in myeloid leukemias. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002287.6. 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
	LAIR1	NM_002287.6	MANE Select	c.386_387delCCinsTT	p.Ser129Phe	missense	N/A	NP_002278.2	Q6GTX8-1
	LAIR1	NM_001289025.3		c.383_384delCCinsTT	p.Ser128Phe	missense	N/A	NP_001275954.2	D3YTC8
	LAIR1	NM_001289026.3		c.365_366delCCinsTT	p.Ser122Phe	missense	N/A	NP_001275955.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAIR1	ENST00000391742.7	TSL:1 MANE Select	c.386_387delCCinsTT	p.Ser129Phe	missense	N/A	ENSP00000375622.2	Q6GTX8-1
	LAIR1	ENST00000348231.8	TSL:1	c.364+865_364+866delCCinsTT		intron	N/A	ENSP00000301193.4	Q6GTX8-2
	LAIR1	ENST00000474878.5	TSL:1	c.361+865_361+866delCCinsTT		intron	N/A	ENSP00000418998.1	Q6GTX8-3

Frequencies

GnomAD3 genomes Cov.: 15

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

GnomAD4 genome Cov.: 15

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.85

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: chr19-54871657;