8-115409261-G-GAAAAAAAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_014112.5(TRPS1):c.*4761_*4762insTTTTTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.36 (7429 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: TRPS1 NM_014112.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: -0.0190

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPS1	NM_014112.5	c.*4761_*4762insTTTTTTTT		3_prime_UTR_variant	7/7	ENST00000395715.8
TRPS1	NM_001282902.3	c.*4761_*4762insTTTTTTTT		3_prime_UTR_variant	6/6
TRPS1	NM_001282903.3	c.*4761_*4762insTTTTTTTT		3_prime_UTR_variant	7/7
TRPS1	NM_001330599.2	c.*4761_*4762insTTTTTTTT		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPS1	ENST00000395715.8	c.*4761_*4762insTTTTTTTT		3_prime_UTR_variant	7/7	1	NM_014112.5	A1
TRPS1	ENST00000640765.1	c.*4761_*4762insTTTTTTTT		3_prime_UTR_variant	6/6	2		P4

Frequencies

GnomAD3 genomes AF: 0.364 AC: 36780 AN: 100920 Hom.: 7429 Cov.: 0

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.327

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.364 AC: 36783 AN: 100914 Hom.: 7429 Cov.: 0 AF XY: 0.355 AC XY: 16347 AN XY: 46052

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.388

Gnomad4 ASJ AF: 0.331

Gnomad4 EAS AF: 0.657

Gnomad4 SAS AF: 0.434

Gnomad4 FIN AF: 0.215

Gnomad4 NFE AF: 0.417

Gnomad4 OTH AF: 0.327

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

Submissions by phenotype

Trichorhinophalangeal syndrome Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

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: rs755990611; hg19: chr8-116421489;