rs35329862

Positions:

• chr8-115623645-T-TA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_014112.5(TRPS1):​c.-9dupT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 1,610,756 control chromosomes in the GnomAD database, including 119,228 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (9057 hom., cov: 0)
  • Exomes 𝑓: 0.38 (110171 hom.)
• Consequence: TRPS1 NM_014112.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 2.50

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 8-115623645-T-TA is Benign according to our data. Variant chr8-115623645-T-TA is described in ClinVar as [Benign]. Clinvar id is 260329.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPS1	NM_014112.5	c.-9dupT		5_prime_UTR_variant	2/7	ENST00000395715.8	NP_054831.2
TRPS1	NM_001282903.3	c.-16dupT		5_prime_UTR_variant	2/7		NP_001269832.1
TRPS1	NM_001282902.3	c.11-3586dupT		intron_variant			NP_001269831.1
TRPS1	NM_001330599.2	c.-2-3586dupT		intron_variant			NP_001317528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPS1	ENST00000395715.8	c.-9dupT		5_prime_UTR_variant	2/7	1	NM_014112.5	ENSP00000379065.3

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48059 AN: 151748 Hom.: 9061 Cov.: 0

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.376

GnomAD3 exomes AF: 0.372 AC: 91534 AN: 246326 Hom.: 18100 AF XY: 0.383 AC XY: 51218 AN XY: 133716

Gnomad AFR exome AF: 0.0978

Gnomad AMR exome AF: 0.287

Gnomad ASJ exome AF: 0.443

Gnomad EAS exome AF: 0.506

Gnomad SAS exome AF: 0.416

Gnomad FIN exome AF: 0.398

Gnomad NFE exome AF: 0.389

Gnomad OTH exome AF: 0.403

GnomAD4 exome AF: 0.384 AC: 560402 AN: 1458888 Hom.: 110171 Cov.: 33 AF XY: 0.387 AC XY: 281039 AN XY: 725724

Gnomad4 AFR exome AF: 0.103

Gnomad4 AMR exome AF: 0.299

Gnomad4 ASJ exome AF: 0.443

Gnomad4 EAS exome AF: 0.444

Gnomad4 SAS exome AF: 0.412

Gnomad4 FIN exome AF: 0.400

Gnomad4 NFE exome AF: 0.388

Gnomad4 OTH exome AF: 0.393

GnomAD4 genome AF: 0.316 AC: 48044 AN: 151868 Hom.: 9057 Cov.: 0 AF XY: 0.321 AC XY: 23854 AN XY: 74206

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.449

Gnomad4 EAS AF: 0.506

Gnomad4 SAS AF: 0.417

Gnomad4 FIN AF: 0.399

Gnomad4 NFE AF: 0.391

Gnomad4 OTH AF: 0.377

Alfa AF: 0.367 Hom.: 2230

Bravo AF: 0.303

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 24, 2015	- -

Trichorhinophalangeal dysplasia type I Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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

Other links and lift over

dbSNP: rs35329862; hg19: chr8-116635872;