rs4129190

Variant names:

• chr2-88173272-G-A
• rs4129190
• NM_018271.5:c.122G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-88173272-G-A
• chr2-88173272-G-T

Variant summary

Our verdict is Benign. The variant received -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. 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.

• 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
• Publications: 33 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: Benign. The variant received -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.

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.122G>A	p.Gly41Glu	missense	Exon 2 of 9	NP_060741.3
	THNSL2	NM_001244676.2		c.122G>A	p.Gly41Glu	missense	Exon 2 of 9	NP_001231605.1	Q86YJ6-2
	THNSL2	NM_001384383.1		c.122G>A	p.Gly41Glu	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.122G>A	p.Gly41Glu	missense	Exon 2 of 9	ENSP00000501453.1	Q86YJ6-1
	THNSL2	ENST00000324166.7	TSL:1	c.122G>A	p.Gly41Glu	missense	Exon 1 of 8	ENSP00000327323.5	Q86YJ6-1
	THNSL2	ENST00000343544.8	TSL:1	c.122G>A	p.Gly41Glu	missense	Exon 2 of 9	ENSP00000339563.4	Q86YJ6-2

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

GnomAD2 exomes AF: 0.850 AC: 213413 AN: 251112 AF XY: 0.853

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 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

African (AFR) AF: 0.920 AC: 30763 AN: 33426

American (AMR) AF: 0.752 AC: 33589 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.908 AC: 23718 AN: 26128

East Asian (EAS) AF: 0.819 AC: 32520 AN: 39684

South Asian (SAS) AF: 0.867 AC: 74684 AN: 86154

European-Finnish (FIN) AF: 0.872 AC: 46551 AN: 53376

Middle Eastern (MID) AF: 0.906 AC: 4021 AN: 4436

European-Non Finnish (NFE) AF: 0.844 AC: 938359 AN: 1111808

Other (OTH) AF: 0.857 AC: 51585 AN: 60226

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

African (AFR) AF: 0.914 AC: 37966 AN: 41550

American (AMR) AF: 0.813 AC: 12446 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.906 AC: 3145 AN: 3472

East Asian (EAS) AF: 0.845 AC: 4361 AN: 5160

South Asian (SAS) AF: 0.871 AC: 4207 AN: 4830

European-Finnish (FIN) AF: 0.872 AC: 9249 AN: 10606

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.854 AC: 58094 AN: 68022

Other (OTH) AF: 0.883 AC: 1865 AN: 2112

Alfa AF: 0.861 Hom.: 249338

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 v4.9

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
MetaRNN	Benign	9.0e-7	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.5	N
PhyloP100		2.3
PrimateAI	Benign	0.36	T
PROVEAN	Benign	1.7	N
REVEL	Benign	0.091
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.029
MPC		0.11
ClinPred		0.0014	T
GERP RS		4.2
PromoterAI		0.0012	Neutral
Varity_R		0.069
gMVP		0.27
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4129190; hg19: chr2-88472791; COSMIC: COSV107404158; COSMIC: COSV107404158;