2-88173329-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018271.5(THNSL2):​c.179C>A​(p.Ala60Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,306 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

THNSL2
NM_018271.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.45
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.03106156).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
THNSL2NM_018271.5 linkuse as main transcriptc.179C>A p.Ala60Asp missense_variant 2/9 ENST00000674334.2 NP_060741.3 Q86YJ6-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
THNSL2ENST00000674334.2 linkuse as main transcriptc.179C>A p.Ala60Asp missense_variant 2/9 NM_018271.5 ENSP00000501453.1 Q86YJ6-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152188
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000400
AC:
1
AN:
249914
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135148
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
34
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152306
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74462
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000653
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMar 29, 2022The c.179C>A (p.A60D) alteration is located in exon 1 (coding exon 1) of the THNSL2 gene. This alteration results from a C to A substitution at nucleotide position 179, causing the alanine (A) at amino acid position 60 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
15
DANN
Uncertain
0.99
DEOGEN2
Benign
0.039
.;.;.;T
Eigen
Benign
-0.45
Eigen_PC
Benign
-0.42
FATHMM_MKL
Benign
0.19
N
LIST_S2
Benign
0.83
T;T;T;T
M_CAP
Benign
0.0087
T
MetaRNN
Benign
0.031
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.2
.;.;L;L
MutationTaster
Benign
1.0
N;N;N;N;N;N
PrimateAI
Benign
0.30
T
PROVEAN
Benign
-0.93
N;N;N;N
REVEL
Benign
0.046
Sift
Benign
0.069
T;T;T;T
Sift4G
Benign
0.57
T;T;T;T
Polyphen
0.36, 0.31, 0.078
.;B;B;B
Vest4
0.29, 0.22, 0.17
MutPred
0.36
Gain of methylation at K56 (P = 0.1294);.;Gain of methylation at K56 (P = 0.1294);Gain of methylation at K56 (P = 0.1294);
MVP
0.15
MPC
0.14
ClinPred
0.079
T
GERP RS
3.5
Varity_R
0.28
gMVP
0.58

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs527305520; hg19: chr2-88472848; API