chr2-88173272-G-A

Position:

• chr2-88173272-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018271.5(THNSL2):​c.122G>A​(p.Gly41Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.849 in 1,612,190 control chromosomes in the GnomAD database, including 581,644 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.87 (57652 hom., cov: 33)
  • Exomes 𝑓: 0.85 (523992 hom.)
• 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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.029999E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.906 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THNSL2	NM_018271.5	c.122G>A	p.Gly41Glu	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>A	p.Gly41Glu	missense_variant	2/9		NM_018271.5	ENSP00000501453.1

Frequencies

GnomAD3 genomes AF: 0.870 AC: 132296 AN: 152142 Hom.: 57618 Cov.: 33

Gnomad AFR AF: 0.914

Gnomad AMI AF: 0.876

Gnomad AMR AF: 0.814

Gnomad ASJ AF: 0.906

Gnomad EAS AF: 0.846

Gnomad SAS AF: 0.871

Gnomad FIN AF: 0.872

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.854

Gnomad OTH AF: 0.881

GnomAD3 exomes AF: 0.850 AC: 213413 AN: 251112 Hom.: 91078 AF XY: 0.853 AC XY: 115722 AN XY: 135718

Gnomad AFR exome AF: 0.916

Gnomad AMR exome AF: 0.744

Gnomad ASJ exome AF: 0.909

Gnomad EAS exome AF: 0.844

Gnomad SAS exome AF: 0.867

Gnomad FIN exome AF: 0.869

Gnomad NFE exome AF: 0.859

Gnomad OTH exome AF: 0.864

GnomAD4 exome AF: 0.846 AC: 1235790 AN: 1459930 Hom.: 523992 Cov.: 58 AF XY: 0.848 AC XY: 615736 AN XY: 726272

Gnomad4 AFR exome AF: 0.920

Gnomad4 AMR exome AF: 0.752

Gnomad4 ASJ exome AF: 0.908

Gnomad4 EAS exome AF: 0.819

Gnomad4 SAS exome AF: 0.867

Gnomad4 FIN exome AF: 0.872

Gnomad4 NFE exome AF: 0.844

Gnomad4 OTH exome AF: 0.857

GnomAD4 genome AF: 0.869 AC: 132387 AN: 152260 Hom.: 57652 Cov.: 33 AF XY: 0.870 AC XY: 64778 AN XY: 74440

Gnomad4 AFR AF: 0.914

Gnomad4 AMR AF: 0.813

Gnomad4 ASJ AF: 0.906

Gnomad4 EAS AF: 0.845

Gnomad4 SAS AF: 0.871

Gnomad4 FIN AF: 0.872

Gnomad4 NFE AF: 0.854

Gnomad4 OTH AF: 0.883

Alfa AF: 0.862 Hom.: 133075

Bravo AF: 0.864

TwinsUK AF: 0.838 AC: 3108

ALSPAC AF: 0.839 AC: 3235

ESP6500AA AF: 0.915 AC: 4033

ESP6500EA AF: 0.857 AC: 7366

ExAC AF: 0.856 AC: 103944

Asia WGS AF: 0.886 AC: 3080 AN: 3478

EpiCase AF: 0.866

EpiControl AF: 0.874

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	11
DANN	Benign	0.20
DEOGEN2	Benign	0.0062	.;.;.;T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.015	T;T;T;T
MetaRNN	Benign	9.0e-7	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.5	.;.;N;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	1.7	N;N;N;N
REVEL	Benign	0.091
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0	.;B;B;B
Vest4		0.029, 0.028, 0.031
MPC		0.11
ClinPred		0.0014	T
GERP RS		4.2
Varity_R		0.069
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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;