Variant 8-115586991-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_014112.5(TRPS1):c.2700+10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00589 in 1,614,004 control chromosomes in the GnomAD database, including 440 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 231 hom., cov: 33)

Exomes 𝑓: 0.0032 ( 209 hom. )

Consequence

TRPS1
NM_014112.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.88

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 8-115586991-A-G is Benign according to our data. Variant chr8-115586991-A-G is described in ClinVar as [Benign]. Clinvar id is 260330.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
TRPS1	NM_014112.5 linkuse as main transcript	c.2700+10T>C	intron_variant	ENST00000395715.8	NP_054831.2	Q9UHF7-2
TRPS1	NM_001282903.3 linkuse as main transcript	c.2679+10T>C	intron_variant		NP_001269832.1	Q9UHF7
TRPS1	NM_001282902.3 linkuse as main transcript	c.2673+10T>C	intron_variant		NP_001269831.1	Q9UHF7-3
TRPS1	NM_001330599.2 linkuse as main transcript	c.2661+10T>C	intron_variant		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.2700+10T>C		intron_variant		1	NM_014112.5	ENSP00000379065.3		Q9UHF7-2

Frequencies

GnomAD3 genomes

AF:

0.0312

AC:

4751

AN:

152174

Hom.:

228

Cov.:

show subpopulations

Gnomad AFR

AF:

0.109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.0186

GnomAD3 exomes

AF:

0.00821

AC:

2034

AN:

247730

Hom.:

104

AF XY:

0.00585

AC XY:

789

AN XY:

134786

show subpopulations

Gnomad AFR exome

AF:

0.114

Gnomad AMR exome

AF:

0.00690

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000981

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000241

Gnomad OTH exome

AF:

0.00612

GnomAD4 exome

AF:

0.00324

AC:

4730

AN:

1461712

Hom.:

209

Cov.:

AF XY:

0.00273

AC XY:

1986

AN XY:

727160

show subpopulations

Gnomad4 AFR exome

AF:

0.110

Gnomad4 AMR exome

AF:

0.00798

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000336

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000147

Gnomad4 OTH exome

AF:

0.00760

GnomAD4 genome

AF:

0.0314

AC:

4776

AN:

152292

Hom.:

231

Cov.:

AF XY:

0.0303

AC XY:

2258

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.109

Gnomad4 AMR

AF:

0.0118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.0184

Alfa

AF:

0.0169

Hom.:

Bravo

AF:

0.0363

Asia WGS

AF:

0.00664

AC:

AN:

3478

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 24, 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 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

1.0

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