rs35051888

Positions:

• chr2-88182739-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_018271.5(THNSL2):​c.843G>A​(p.Leu281=) 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THNSL2	NM_018271.5	c.843G>A	p.Leu281=	synonymous_variant	6/9	ENST00000674334.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THNSL2	ENST00000674334.2	c.843G>A	p.Leu281=	synonymous_variant	6/9		NM_018271.5	P1

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

GnomAD3 exomes AF: 0.152 AC: 38302 AN: 251386 Hom.: 3782 AF XY: 0.143 AC XY: 19421 AN XY: 135862

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 SAS exome AF: 0.0964

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

Gnomad4 AFR exome AF: 0.0491

Gnomad4 AMR exome AF: 0.297

Gnomad4 ASJ exome AF: 0.0924

Gnomad4 EAS exome AF: 0.186

Gnomad4 SAS exome AF: 0.0935

Gnomad4 FIN exome AF: 0.204

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.119

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

Gnomad4 AFR AF: 0.0549

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.0940

Gnomad4 EAS AF: 0.166

Gnomad4 SAS AF: 0.0870

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.108

Alfa AF: 0.118 Hom.: 581

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	9.6
DANN	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs35051888; hg19: chr2-88482258; COSMIC: COSV59082302;