8-115409269-A-AAAAAAAAC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_014112.5(TRPS1):c.*4753_*4754insGTTTTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00255 in 149,204 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (1 hom., cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TRPS1 NM_014112.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.584

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 -10 ACMG points.

• BP6: Variant 8-115409269-A-AAAAAAAAC is Benign according to our data. Variant chr8-115409269-A-AAAAAAAAC is described in ClinVar as [Likely_benign]. Clinvar id is 2658767.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00255 (381/149204) while in subpopulation AMR AF= 0.00433 (64/14784). AF 95% confidence interval is 0.00348. There are 1 homozygotes in gnomad4. There are 189 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High AC in GnomAd at 381 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPS1	NM_014112.5	c.*4753_*4754insGTTTTTTT		3_prime_UTR_variant	7/7	ENST00000395715.8
TRPS1	NM_001282902.3	c.*4753_*4754insGTTTTTTT		3_prime_UTR_variant	6/6
TRPS1	NM_001282903.3	c.*4753_*4754insGTTTTTTT		3_prime_UTR_variant	7/7
TRPS1	NM_001330599.2	c.*4753_*4754insGTTTTTTT		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPS1	ENST00000395715.8	c.*4753_*4754insGTTTTTTT		3_prime_UTR_variant	7/7	1	NM_014112.5	A1
TRPS1	ENST00000640765.1	c.*4753_*4754insGTTTTTTT		3_prime_UTR_variant	6/6	2		P4

Frequencies

GnomAD3 genomes AF: 0.00255 AC: 381 AN: 149128 Hom.: 1 Cov.: 30

Gnomad AFR AF: 0.000710

Gnomad AMI AF: 0.0254

Gnomad AMR AF: 0.00433

Gnomad ASJ AF: 0.00550

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00155

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00336

Gnomad OTH AF: 0.00196

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.00255 AC: 381 AN: 149204 Hom.: 1 Cov.: 30 AF XY: 0.00260 AC XY: 189 AN XY: 72790

Gnomad4 AFR AF: 0.000708

Gnomad4 AMR AF: 0.00433

Gnomad4 ASJ AF: 0.00550

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000210

Gnomad4 FIN AF: 0.00155

Gnomad4 NFE AF: 0.00336

Gnomad4 OTH AF: 0.00195

Alfa AF: 0.00214 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

TRPS1: BS1 -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1199631166; hg19: chr8-116421497;