Variant rs7823278 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_014112.5(TRPS1):c.423G>T(p.Pro141Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0282 in 1,614,012 control chromosomes in the GnomAD database, including 8,729 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 4548 hom., cov: 32)

Exomes 𝑓: 0.017 ( 4181 hom. )

Consequence

TRPS1
NM_014112.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.41

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 8-115619675-C-A is Benign according to our data. Variant chr8-115619675-C-A is described in ClinVar as [Benign]. Clinvar id is 260333.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.41 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPS1	NM_014112.5 linkuse as main transcript	c.423G>T	p.Pro141Pro	synonymous_variant	3/7	ENST00000395715.8	NP_054831.2	Q9UHF7-2
TRPS1	NM_001282903.3 linkuse as main transcript	c.402G>T	p.Pro134Pro	synonymous_variant	3/7		NP_001269832.1	Q9UHF7
TRPS1	NM_001282902.3 linkuse as main transcript	c.396G>T	p.Pro132Pro	synonymous_variant	2/6		NP_001269831.1	Q9UHF7-3
TRPS1	NM_001330599.2 linkuse as main transcript	c.384G>T	p.Pro128Pro	synonymous_variant	2/6		NP_001317528.1	Q9UHF7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPS1	ENST00000395715.8 linkuse as main transcript	c.423G>T	p.Pro141Pro	synonymous_variant	3/7	1	NM_014112.5	ENSP00000379065.3		Q9UHF7-2

Frequencies

GnomAD3 genomes

AF:

0.135

AC:

20542

AN:

152014

Hom.:

4537

Cov.:

show subpopulations

Gnomad AFR

AF:

0.462

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0539

Gnomad ASJ

AF:

0.00433

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0468

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.00243

Gnomad OTH

AF:

0.0881

GnomAD3 exomes

AF:

0.0405

AC:

10096

AN:

249116

Hom.:

1784

AF XY:

0.0339

AC XY:

4578

AN XY:

135152

show subpopulations

Gnomad AFR exome

AF:

0.473

Gnomad AMR exome

AF:

0.0292

Gnomad ASJ exome

AF:

0.00437

Gnomad EAS exome

AF:

0.000223

Gnomad SAS exome

AF:

0.0436

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00214

Gnomad OTH exome

AF:

0.0232

GnomAD4 exome

AF:

0.0171

AC:

24938

AN:

1461880

Hom.:

4181

Cov.:

AF XY:

0.0163

AC XY:

11871

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.475

Gnomad4 AMR exome

AF:

0.0326

Gnomad4 ASJ exome

AF:

0.00524

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0417

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.00127

Gnomad4 OTH exome

AF:

0.0371

GnomAD4 genome

AF:

0.135

AC:

20596

AN:

152132

Hom.:

4548

Cov.:

AF XY:

0.131

AC XY:

9760

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.462

Gnomad4 AMR

AF:

0.0538

Gnomad4 ASJ

AF:

0.00433

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0464

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00243

Gnomad4 OTH

AF:

0.0872

Alfa

AF:

0.0361

Hom.:

1431

Bravo

AF:

0.152

Asia WGS

AF:

0.0520

AC:

180

AN:

3478

EpiCase

AF:

0.00284

EpiControl

AF:

0.00231

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.69

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