rs35329862

Variant names:

• chr8-115623645-T-TA
• rs35329862
• NM_014112.5:c.-9dupT

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
TRPS1	NM_014112.5	c.-9dupT		5_prime_UTR_variant	Exon 2 of 7	ENST00000395715.8	NP_054831.2
TRPS1	NM_001282903.3	c.-16dupT		5_prime_UTR_variant	Exon 2 of 7		NP_001269832.1
TRPS1	NM_001282902.3	c.11-3586dupT		intron_variant	Intron 1 of 5		NP_001269831.1
TRPS1	NM_001330599.2	c.-2-3586dupT		intron_variant	Intron 1 of 5		NP_001317528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPS1	ENST00000395715.8	c.-9dupT		5_prime_UTR_variant	Exon 2 of 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

GnomAD2 exomes AF: 0.372 AC: 91534 AN: 246326 AF XY: 0.383

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 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

African (AFR) AF: 0.103 AC: 3438 AN: 33422

American (AMR) AF: 0.299 AC: 13331 AN: 44582

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 11545 AN: 26062

East Asian (EAS) AF: 0.444 AC: 17577 AN: 39566

South Asian (SAS) AF: 0.412 AC: 35453 AN: 86076

European-Finnish (FIN) AF: 0.400 AC: 21127 AN: 52788

Middle Eastern (MID) AF: 0.524 AC: 3016 AN: 5756

European-Non Finnish (NFE) AF: 0.388 AC: 431224 AN: 1110420

Other (OTH) AF: 0.393 AC: 23691 AN: 60216

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

African (AFR) AF: 0.106 AC: 4388 AN: 41518

American (AMR) AF: 0.364 AC: 5549 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 1555 AN: 3466

East Asian (EAS) AF: 0.506 AC: 2612 AN: 5164

South Asian (SAS) AF: 0.417 AC: 2011 AN: 4824

European-Finnish (FIN) AF: 0.399 AC: 4209 AN: 10536

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.391 AC: 26491 AN: 67802

Other (OTH) AF: 0.377 AC: 794 AN: 2106

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

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Aug 24, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Trichorhinophalangeal dysplasia type I Benign:1

May 28, 2019

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

May 15, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs35329862; hg19: chr8-116635872; COSMIC: COSV55236309; COSMIC: COSV55236309;