2-88173272-G-T

Position:

• chr2-88173272-G-T

Variant summary

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

The NM_018271.5(THNSL2):​c.122G>T​(p.Gly41Val) 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. G41E) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: THNSL2 NM_018271.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.31

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]

THNSL2 (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=0.1280326).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THNSL2	NM_018271.5	c.122G>T	p.Gly41Val	missense_variant	2/9	ENST00000674334.2	NP_060741.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THNSL2	ENST00000674334.2	c.122G>T	p.Gly41Val	missense_variant	2/9		NM_018271.5	ENSP00000501453.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 58

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	19
DANN	Benign	0.92
DEOGEN2	Benign	0.030	.;.;.;T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.25	T;T;T;T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.13	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	.;.;L;L
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.6	N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.14	T;T;T;T
Sift4G	Benign	0.21	T;T;T;T
Polyphen		0.011, 0.020, 0.0	.;B;B;B
Vest4		0.12, 0.11, 0.084
MutPred		0.42		Loss of loop (P = 0.0112);.;Loss of loop (P = 0.0112);Loss of loop (P = 0.0112);
MVP		0.11
MPC		0.11
ClinPred		0.22	T
GERP RS		4.2
Varity_R		0.11
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs4129190; hg19: chr2-88472791;