rs7823278

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

trichorhinophalangeal syndrome type I
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
trichorhinophalangeal syndrome, type III
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
trichorhinophalangeal syndrome type I or III
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TRPS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein
TRPS1	NM_014112.5 link	c.423G>T	p.Pro141Pro	synonymous_variant	Exon 3 of 7	ENST00000395715.8	NP_054831.2
TRPS1	NM_001282903.3 link	c.402G>T	p.Pro134Pro	synonymous_variant	Exon 3 of 7		NP_001269832.1
TRPS1	NM_001282902.3 link	c.396G>T	p.Pro132Pro	synonymous_variant	Exon 2 of 6		NP_001269831.1
TRPS1	NM_001330599.2 link	c.384G>T	p.Pro128Pro	synonymous_variant	Exon 2 of 6		NP_001317528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPS1	ENST00000395715.8 link	c.423G>T	p.Pro141Pro	synonymous_variant	Exon 3 of 7	1	NM_014112.5	ENSP00000379065.3

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

GnomAD2 exomes

AF:

0.0405

AC:

10096

AN:

249116

AF XY:

0.0339

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 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

African (AFR)

AF:

0.475

AC:

15902

AN:

33480

American (AMR)

AF:

0.0326

AC:

1458

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00524

AC:

137

AN:

26134

East Asian (EAS)

AF:

0.000151

AC:

AN:

39698

South Asian (SAS)

AF:

0.0417

AC:

3598

AN:

86256

European-Finnish (FIN)

AF:

0.0000374

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.0319

AC:

184

AN:

5768

European-Non Finnish (NFE)

AF:

0.00127

AC:

1411

AN:

1112006

Other (OTH)

AF:

0.0371

AC:

2240

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

1230

2461

3691

4922

6152

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

472

944

1416

1888

2360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.135

AC:

20596

AN:

152132

Hom.:

4548

Cov.:

AF XY:

0.131

AC XY:

9760

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.462

AC:

19166

AN:

41450

American (AMR)

AF:

0.0538

AC:

823

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00433

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.0464

AC:

224

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00243

AC:

165

AN:

68006

Other (OTH)

AF:

0.0872

AC:

184

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

573

1145

1718

2290

2863

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

174

348

522

696

870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0504

Hom.:

2576

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

May 05, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.69

PhyloP100

3.4

PromoterAI

-0.0065

Neutral

(source)

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over