rs1554617078

Positions:

• chr8-115415048-C-CGTTGTTTT

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The NM_014112.5(TRPS1):​c.2852_2859dupAAAACAAC​(p.Gly954fs) 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 NM_014112.5 frameshift
• Clinical Significance: not provided no classification provided O:1
• 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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 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. Fraction of 0.264 CDS is truncated, and there are 1 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.2852_2859dupAAAACAAC	p.Gly954fs	frameshift_variant	7/7	ENST00000395715.8	NP_054831.2
TRPS1	NM_001282903.3	c.2831_2838dupAAAACAAC	p.Gly947fs	frameshift_variant	7/7		NP_001269832.1
TRPS1	NM_001282902.3	c.2825_2832dupAAAACAAC	p.Gly945fs	frameshift_variant	6/6		NP_001269831.1
TRPS1	NM_001330599.2	c.2813_2820dupAAAACAAC	p.Gly941fs	frameshift_variant	6/6		NP_001317528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPS1	ENST00000395715.8	c.2852_2859dupAAAACAAC	p.Gly954fs	frameshift_variant	7/7	1	NM_014112.5	ENSP00000379065.3

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

Submissions by phenotype

Trichorhinophalangeal dysplasia type I Other:1

not provided, no classification provided

literature only

GeneReviews

-

- -

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: rs1554617078; hg19: chr8-116427276;