2-88173272-GG-AA

Variant names:

• chr2-88173272-GG-AA
• NM_018271.5:c.122_123delGGinsAA
• THNSL2 p.Gly41Glu

Variant summary

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

The NM_018271.5(THNSL2):​c.122_123delGGinsAA​(p.Gly41Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. The variant is present in control chromosomes in GnomAd MNV project. The variant allele was found at a frequency of 0.00000708 in 2 alleles, including 0 homozygotes. 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: GnomAD MNV: 𝑓 0.0000071 Genomes: not found (cov: 33)
• Consequence: THNSL2 NM_018271.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.31
• Publications: 0 publications found

Genes affected

THNSL2 (HGNC:25602): (threonine synthase like 2) This gene encodes a threonine synthase-like protein. A similar enzyme in mouse can catalyze the degradation of O-phospho-homoserine to a-ketobutyrate, phosphate, and ammonia. This protein also has phospho-lyase activity on both gamma and beta phosphorylated substrates. In mouse an alternatively spliced form of this protein has been shown to act as a cytokine and can induce the production of the inflammatory cytokine IL6 in osteoblasts. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2011]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018271.5. 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
	THNSL2	NM_018271.5	MANE Select	c.122_123delGGinsAA	p.Gly41Glu	missense	N/A	NP_060741.3
	THNSL2	NM_001244676.2		c.122_123delGGinsAA	p.Gly41Glu	missense	N/A	NP_001231605.1	Q86YJ6-2
	THNSL2	NM_001384383.1		c.122_123delGGinsAA	p.Gly41Glu	missense	N/A	NP_001371312.1	Q86YJ6-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THNSL2	ENST00000674334.2	MANE Select	c.122_123delGGinsAA	p.Gly41Glu	missense	N/A	ENSP00000501453.1	Q86YJ6-1
	THNSL2	ENST00000324166.7	TSL:1	c.122_123delGGinsAA	p.Gly41Glu	missense	N/A	ENSP00000327323.5	Q86YJ6-1
	THNSL2	ENST00000343544.8	TSL:1	c.122_123delGGinsAA	p.Gly41Glu	missense	N/A	ENSP00000339563.4	Q86YJ6-2

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

GnomAD MNV AF: 0.00000708 AC: 2 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.3

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: chr2-88472791;