Variant 18-9359992-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_020648.6(TWSG1):c.144G>A(p.Pro48=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00575 in 1,613,184 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0049 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0058 ( 50 hom. )

Consequence

TWSG1
NM_020648.6 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.971

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]

TWSG1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 18-9359992-G-A is Benign according to our data. Variant chr18-9359992-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2648565.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.971 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00584 (8536/1460940) while in subpopulation MID AF= 0.0352 (203/5762). AF 95% confidence interval is 0.0313. There are 50 homozygotes in gnomad4_exome. There are 4353 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TWSG1	NM_020648.6 linkuse as main transcript	c.144G>A	p.Pro48=	synonymous_variant	3/5	ENST00000262120.10	NP_065699.1
TWSG1	XM_047437675.1 linkuse as main transcript	c.-34G>A		5_prime_UTR_variant	2/4		XP_047293631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TWSG1	ENST00000262120.10 linkuse as main transcript	c.144G>A	p.Pro48=	synonymous_variant	3/5	1	NM_020648.6	ENSP00000262120	P1	Q9GZX9-1
TWSG1	ENST00000581641.1 linkuse as main transcript	c.144G>A	p.Pro48=	synonymous_variant	3/4	2		ENSP00000464458
TWSG1	ENST00000583147.5 linkuse as main transcript	c.144G>A	p.Pro48=	synonymous_variant, NMD_transcript_variant	3/7	2		ENSP00000463331		Q9GZX9-2

Frequencies

GnomAD3 genomes

AF:

0.00488

AC:

743

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00135

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00714

Gnomad ASJ

AF:

0.0205

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.00673

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.00547

AC:

1374

AN:

251324

Hom.:

AF XY:

0.00580

AC XY:

788

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.00466

Gnomad ASJ exome

AF:

0.0221

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00405

Gnomad FIN exome

AF:

0.000508

Gnomad NFE exome

AF:

0.00689

Gnomad OTH exome

AF:

0.00734

GnomAD4 exome

AF:

0.00584

AC:

8536

AN:

1460940

Hom.:

Cov.:

AF XY:

0.00599

AC XY:

4353

AN XY:

726776

show subpopulations

Gnomad4 AFR exome

AF:

0.00182

Gnomad4 AMR exome

AF:

0.00494

Gnomad4 ASJ exome

AF:

0.0221

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00436

Gnomad4 FIN exome

AF:

0.000525

Gnomad4 NFE exome

AF:

0.00595

Gnomad4 OTH exome

AF:

0.00754

GnomAD4 genome

AF:

0.00487

AC:

741

AN:

152244

Hom.:

Cov.:

AF XY:

0.00439

AC XY:

327

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00132

Gnomad4 AMR

AF:

0.00713

Gnomad4 ASJ

AF:

0.0205

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00270

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00673

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.00734

Hom.:

Bravo

AF:

0.00519

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.00902

EpiControl

AF:

0.0103

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

TWSG1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.3

DANN

Benign

0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over