2-88174697-G-C

Position:

• chr2-88174697-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018271.5(THNSL2):​c.282G>C​(p.Arg94Ser) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: THNSL2 NM_018271.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.60

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4053988).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THNSL2	NM_018271.5	c.282G>C	p.Arg94Ser	missense_variant	3/9	ENST00000674334.2	NP_060741.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THNSL2	ENST00000674334.2	c.282G>C	p.Arg94Ser	missense_variant	3/9		NM_018271.5	ENSP00000501453.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 14, 2024

The c.282G>C (p.R94S) alteration is located in exon 2 (coding exon 2) of the THNSL2 gene. This alteration results from a G to C substitution at nucleotide position 282, causing the arginine (R) at amino acid position 94 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.046	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	.;.;.;T
Eigen	Benign	0.14
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.87	D;D;D;D
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.41	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	.;.;L;L
MutationTaster	Benign	0.89	D;D;D;D;D;D
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.5	D;D;D;D
REVEL	Benign	0.14
Sift	Uncertain	0.0050	D;T;T;T
Sift4G	Benign	0.12	T;T;T;D
Polyphen		0.92, 0.90, 0.77	.;P;P;P
Vest4		0.65, 0.67, 0.67
MutPred		0.56		Loss of MoRF binding (P = 0.0169);.;Loss of MoRF binding (P = 0.0169);Loss of MoRF binding (P = 0.0169);
MVP		0.17
MPC		0.30
ClinPred		0.97	D
GERP RS		4.8
Varity_R		0.29
gMVP		0.61

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-88474216;