rs1554617078
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The ENST00000395715.8(TRPS1):c.2859_2860insAAAACAAC(p.Gly954LysfsTer43) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as not provided (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
TRPS1
ENST00000395715.8 frameshift
ENST00000395715.8 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.60
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 20 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TRPS1 | NM_014112.5 | c.2859_2860insAAAACAAC | p.Gly954LysfsTer43 | frameshift_variant | 7/7 | ENST00000395715.8 | NP_054831.2 | |
TRPS1 | NM_001282902.3 | c.2832_2833insAAAACAAC | p.Gly945LysfsTer43 | frameshift_variant | 6/6 | NP_001269831.1 | ||
TRPS1 | NM_001282903.3 | c.2838_2839insAAAACAAC | p.Gly947LysfsTer43 | frameshift_variant | 7/7 | NP_001269832.1 | ||
TRPS1 | NM_001330599.2 | c.2820_2821insAAAACAAC | p.Gly941LysfsTer43 | frameshift_variant | 6/6 | NP_001317528.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TRPS1 | ENST00000395715.8 | c.2859_2860insAAAACAAC | p.Gly954LysfsTer43 | frameshift_variant | 7/7 | 1 | NM_014112.5 | ENSP00000379065 | A1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link
Submissions by phenotype
Trichorhinophalangeal dysplasia type I Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at