18-9399458-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_020648.6(TWSG1):​c.603C>T​(p.Cys201Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000387 in 1,613,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00091 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00033 ( 0 hom. )

Consequence

TWSG1
NM_020648.6 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.57
Variant links:
Genes affected
TWSG1 (HGNC:12429): (twisted gastrulation BMP signaling modulator 1) Enables transforming growth factor beta binding activity. Involved in several processes, including negative regulation of CD4-positive, alpha-beta T cell proliferation; positive regulation of pathway-restricted SMAD protein phosphorylation; and transforming growth factor beta receptor signaling pathway. Predicted to be located in extracellular region. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.32).
BP6
Variant 18-9399458-C-T is Benign according to our data. Variant chr18-9399458-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2648566.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-1.57 with no splicing effect.
BS2
High AC in GnomAd4 at 138 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TWSG1NM_020648.6 linkc.603C>T p.Cys201Cys synonymous_variant Exon 5 of 5 ENST00000262120.10 NP_065699.1 Q9GZX9-1
TWSG1XM_047437675.1 linkc.426C>T p.Cys142Cys synonymous_variant Exon 4 of 4 XP_047293631.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TWSG1ENST00000262120.10 linkc.603C>T p.Cys201Cys synonymous_variant Exon 5 of 5 1 NM_020648.6 ENSP00000262120.5 Q9GZX9-1
TWSG1ENST00000583147.5 linkn.*533C>T non_coding_transcript_exon_variant Exon 7 of 7 2 ENSP00000463331.1 Q9GZX9-2
TWSG1ENST00000583147.5 linkn.*533C>T 3_prime_UTR_variant Exon 7 of 7 2 ENSP00000463331.1 Q9GZX9-2

Frequencies

GnomAD3 genomes
AF:
0.000868
AC:
132
AN:
152126
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00162
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00157
Gnomad ASJ
AF:
0.00144
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000500
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000541
AC:
136
AN:
251218
Hom.:
0
AF XY:
0.000486
AC XY:
66
AN XY:
135764
show subpopulations
Gnomad AFR exome
AF:
0.00166
Gnomad AMR exome
AF:
0.00101
Gnomad ASJ exome
AF:
0.00129
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000475
Gnomad OTH exome
AF:
0.00114
GnomAD4 exome
AF:
0.000332
AC:
486
AN:
1461694
Hom.:
0
Cov.:
31
AF XY:
0.000336
AC XY:
244
AN XY:
727166
show subpopulations
Gnomad4 AFR exome
AF:
0.00173
Gnomad4 AMR exome
AF:
0.00101
Gnomad4 ASJ exome
AF:
0.000880
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000255
Gnomad4 OTH exome
AF:
0.000928
GnomAD4 genome
AF:
0.000906
AC:
138
AN:
152244
Hom.:
0
Cov.:
32
AF XY:
0.000752
AC XY:
56
AN XY:
74440
show subpopulations
Gnomad4 AFR
AF:
0.00176
Gnomad4 AMR
AF:
0.00157
Gnomad4 ASJ
AF:
0.00144
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000500
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000701
Hom.:
0
Bravo
AF:
0.000839
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000273
EpiControl
AF:
0.000356

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Jan 01, 2023
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

TWSG1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.32
CADD
Benign
2.4
DANN
Benign
0.54
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs138769456; hg19: chr18-9399456; COSMIC: COSV50815882; COSMIC: COSV50815882; API