2-88173239-T-C

Variant names:

• chr2-88173239-T-C
• NM_018271.5:c.89T>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_018271.5(THNSL2):​c.89T>C​(p.Phe30Ser) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: THNSL2 NM_018271.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.99
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.879

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.89T>C	p.Phe30Ser	missense	Exon 2 of 9	NP_060741.3
	THNSL2	NM_001244676.2		c.89T>C	p.Phe30Ser	missense	Exon 2 of 9	NP_001231605.1	Q86YJ6-2
	THNSL2	NM_001384383.1		c.89T>C	p.Phe30Ser	missense	Exon 1 of 7	NP_001371312.1	Q86YJ6-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THNSL2	ENST00000674334.2	MANE Select	c.89T>C	p.Phe30Ser	missense	Exon 2 of 9	ENSP00000501453.1	Q86YJ6-1
	THNSL2	ENST00000324166.7	TSL:1	c.89T>C	p.Phe30Ser	missense	Exon 1 of 8	ENSP00000327323.5	Q86YJ6-1
	THNSL2	ENST00000343544.8	TSL:1	c.89T>C	p.Phe30Ser	missense	Exon 2 of 9	ENSP00000339563.4	Q86YJ6-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Uncertain	0.094	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Benign	0.14
Eigen_PC	Benign	-0.017
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.048	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Benign	-0.48	T
MutationAssessor	Pathogenic	3.6	H
PhyloP100		2.0
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0060	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.98	D
Vest4		0.55
MutPred		0.76		Gain of disorder (P = 0.001)
MVP		0.46
MPC		0.40
ClinPred		0.99	D
GERP RS		-0.24
PromoterAI		-0.010	Neutral
Varity_R		0.68
gMVP		0.87
Mutation Taster		=68/32	polymorphism

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

Other links and lift over

hg19: chr2-88472758;