rs1554617549

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2

The NM_014112.5(TRPS1):​c.2823+1G>T variant causes a splice donor, intron change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

TRPS1
NM_014112.5 splice_donor, intron

Scores

4
2
1
Splicing: ADA: 1.000
2

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 7.71
Variant links:
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 Uncertain_significance. Variant got 4 ACMG points.

PVS1
Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.03140283 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TRPS1NM_014112.5 linkuse as main transcriptc.2823+1G>T splice_donor_variant, intron_variant ENST00000395715.8 NP_054831.2 Q9UHF7-2
TRPS1NM_001282903.3 linkuse as main transcriptc.2802+1G>T splice_donor_variant, intron_variant NP_001269832.1 Q9UHF7
TRPS1NM_001282902.3 linkuse as main transcriptc.2796+1G>T splice_donor_variant, intron_variant NP_001269831.1 Q9UHF7-3
TRPS1NM_001330599.2 linkuse as main transcriptc.2784+1G>T splice_donor_variant, intron_variant NP_001317528.1 Q9UHF7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TRPS1ENST00000395715.8 linkuse as main transcriptc.2823+1G>T splice_donor_variant, intron_variant 1 NM_014112.5 ENSP00000379065.3 Q9UHF7-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
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 providedliterature onlyGeneReviews-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.63
D
BayesDel_noAF
Pathogenic
0.28
CADD
Pathogenic
34
DANN
Uncertain
0.99
Eigen
Pathogenic
1.2
Eigen_PC
Pathogenic
1.1
FATHMM_MKL
Uncertain
0.94
D
GERP RS
5.8

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
1.0
dbscSNV1_RF
Pathogenic
0.94
SpliceAI score (max)
1.0
Details are displayed if max score is > 0.2
DS_DL_spliceai
1.0
Position offset: 1

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1554617549; hg19: chr8-116430557; API