NM_018271.5:c.843G>A

Variant names:

• chr2-88182739-G-A
• rs35051888
• NM_018271.5:c.843G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_018271.5(THNSL2):​c.843G>A​(p.Leu281Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,613,850 control chromosomes in the GnomAD database, including 15,189 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (1409 hom., cov: 32)
  • Exomes 𝑓: 0.13 (13780 hom.)
• Consequence: THNSL2 NM_018271.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.595
• Publications: 15 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP7: Synonymous conserved (PhyloP=0.595 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.207 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THNSL2	NM_018271.5	MANE Select	c.843G>A	p.Leu281Leu	synonymous	Exon 6 of 9	NP_060741.3
	THNSL2	NM_001244676.2		c.843G>A	p.Leu281Leu	synonymous	Exon 6 of 9	NP_001231605.1
	THNSL2	NM_001384383.1		c.843G>A	p.Leu281Leu	synonymous	Exon 5 of 7	NP_001371312.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THNSL2	ENST00000674334.2	MANE Select	c.843G>A	p.Leu281Leu	synonymous	Exon 6 of 9	ENSP00000501453.1
	THNSL2	ENST00000324166.7	TSL:1	c.843G>A	p.Leu281Leu	synonymous	Exon 5 of 8	ENSP00000327323.5
	THNSL2	ENST00000343544.8	TSL:1	c.843G>A	p.Leu281Leu	synonymous	Exon 6 of 9	ENSP00000339563.4

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18419 AN: 152032 Hom.: 1401 Cov.: 32

Gnomad AFR AF: 0.0550

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.0940

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.0863

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.109

GnomAD2 exomes AF: 0.152 AC: 38302 AN: 251386 AF XY: 0.143

Gnomad AFR exome AF: 0.0504

Gnomad AMR exome AF: 0.310

Gnomad ASJ exome AF: 0.0946

Gnomad EAS exome AF: 0.159

Gnomad FIN exome AF: 0.210

Gnomad NFE exome AF: 0.128

Gnomad OTH exome AF: 0.142

GnomAD4 exome AF: 0.130 AC: 190002 AN: 1461700 Hom.: 13780 Cov.: 31 AF XY: 0.128 AC XY: 92855 AN XY: 727134

African (AFR) AF: 0.0491 AC: 1643 AN: 33478

American (AMR) AF: 0.297 AC: 13275 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0924 AC: 2414 AN: 26128

East Asian (EAS) AF: 0.186 AC: 7380 AN: 39698

South Asian (SAS) AF: 0.0935 AC: 8066 AN: 86246

European-Finnish (FIN) AF: 0.204 AC: 10906 AN: 53410

Middle Eastern (MID) AF: 0.0624 AC: 360 AN: 5768

European-Non Finnish (NFE) AF: 0.125 AC: 138778 AN: 1111870

Other (OTH) AF: 0.119 AC: 7180 AN: 60384

GnomAD4 genome AF: 0.121 AC: 18439 AN: 152150 Hom.: 1409 Cov.: 32 AF XY: 0.124 AC XY: 9214 AN XY: 74370

African (AFR) AF: 0.0549 AC: 2278 AN: 41520

American (AMR) AF: 0.213 AC: 3256 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0940 AC: 326 AN: 3468

East Asian (EAS) AF: 0.166 AC: 858 AN: 5170

South Asian (SAS) AF: 0.0870 AC: 419 AN: 4814

European-Finnish (FIN) AF: 0.207 AC: 2183 AN: 10570

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8654 AN: 68008

Other (OTH) AF: 0.108 AC: 228 AN: 2110

Alfa AF: 0.121 Hom.: 808

Bravo AF: 0.123

Asia WGS AF: 0.125 AC: 435 AN: 3478

EpiCase AF: 0.107

EpiControl AF: 0.110

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	9.6
DANN	Benign	0.73
PhyloP100		0.59
Mutation Taster		=93/7	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs35051888; hg19: chr2-88482258; COSMIC: COSV59082302;