Variant rs191525942 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The ENST00000395715.8(TRPS1):c.2658G>T(p.Ser886=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00105 in 1,614,180 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 5 hom. )

Consequence

TRPS1
ENST00000395715.8 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.90

Variant links:

Genes affected

TRPS1 (HGNC:12340): (transcriptional repressor GATA binding 1) This gene encodes a transcription factor that represses GATA-regulated genes and binds to a dynein light chain protein. Binding of the encoded protein to the dynein light chain protein affects binding to GATA consensus sequences and suppresses its transcriptional activity. Defects in this gene are a cause of tricho-rhino-phalangeal syndrome (TRPS) types I-III. [provided by RefSeq, Jul 2008]

TRPS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 8-115587043-C-A is Benign according to our data. Variant chr8-115587043-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 361613.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.9 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00148 (226/152340) while in subpopulation NFE AF= 0.00121 (82/68036). AF 95% confidence interval is 0.000994. There are 2 homozygotes in gnomad4. There are 150 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 226 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TRPS1	NM_014112.5 linkuse as main transcript	c.2658G>T	p.Ser886=	synonymous_variant	5/7	ENST00000395715.8	NP_054831.2
TRPS1	NM_001282903.3 linkuse as main transcript	c.2637G>T	p.Ser879=	synonymous_variant	5/7		NP_001269832.1
TRPS1	NM_001282902.3 linkuse as main transcript	c.2631G>T	p.Ser877=	synonymous_variant	4/6		NP_001269831.1
TRPS1	NM_001330599.2 linkuse as main transcript	c.2619G>T	p.Ser873=	synonymous_variant	4/6		NP_001317528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPS1	ENST00000395715.8 linkuse as main transcript	c.2658G>T	p.Ser886=	synonymous_variant	5/7	1	NM_014112.5	ENSP00000379065	A1	Q9UHF7-2

Frequencies

GnomAD3 genomes

AF:

0.00148

AC:

226

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0130

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00121

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00200

AC:

499

AN:

248920

Hom.:

AF XY:

0.00193

AC XY:

261

AN XY:

135194

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0135

Gnomad NFE exome

AF:

0.00179

Gnomad OTH exome

AF:

0.000661

GnomAD4 exome

AF:

0.00101

AC:

1470

AN:

1461840

Hom.:

Cov.:

AF XY:

0.000965

AC XY:

702

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0117

Gnomad4 NFE exome

AF:

0.000695

Gnomad4 OTH exome

AF:

0.00116

GnomAD4 genome

AF:

0.00148

AC:

226

AN:

152340

Hom.:

Cov.:

AF XY:

0.00201

AC XY:

150

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0130

Gnomad4 NFE

AF:

0.00121

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000747

Hom.:

Bravo

AF:

0.000499

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000763

EpiControl

AF:

0.000830

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2023

TRPS1: BP4, BP7 -

TRPS1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 26, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Trichorhinophalangeal dysplasia type I;C1860823:Trichorhinophalangeal syndrome, type III

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 02, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.11

DANN

Benign

0.71

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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.

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