dbSNP rs4129190: THNSL2:p.Gly41Glu (chr2-88173272-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.31

Publications

33 publications found

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THNSL2	NM_018271.5 link	c.122G>A	p.Gly41Glu	missense_variant	Exon 2 of 9	ENST00000674334.2	NP_060741.3	Q86YJ6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THNSL2	ENST00000674334.2 link	c.122G>A	p.Gly41Glu	missense_variant	Exon 2 of 9		NM_018271.5	ENSP00000501453.1		Q86YJ6-1

Frequencies

GnomAD3 genomes

AF:

0.870

AC:

132296

AN:

152142

Hom.:

57618

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.848

AC XY:

615736

AN XY:

726272

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

10379

20757

31136

41514

51893

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21080

42160

63240

84320

105400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.869

AC:

132387

AN:

152260

Hom.:

57652

Cov.:

AF XY:

0.870

AC XY:

64778

AN XY:

74440

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

891

1781

2672

3562

4453

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

894

1788

2682

3576

4470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.20

DEOGEN2

Benign

0.0062

.;.;.;T

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.015

T;T;T;T

MetaRNN

Benign

9.0e-7

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.5

.;.;N;N

PhyloP100

2.3

PrimateAI

Benign

0.36

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

GERP RS

4.2

PromoterAI

0.0012

Neutral

(source)

Varity_R

0.069

gMVP

0.27

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over