rs179442

Variant names:

• chr8-115657542-C-T
• rs179442
• NM_014112.5:c.-122+11003G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014112.5(TRPS1):​c.-122+11003G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 151,814 control chromosomes in the GnomAD database, including 17,920 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.46 (17920 hom., cov: 32)
• Consequence: TRPS1 NM_014112.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.460
• Publications: 7 publications found

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]

TRPS1 Gene-Disease associations (from GenCC):

• trichorhinophalangeal syndrome type I

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• trichorhinophalangeal syndrome, type III

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• trichorhinophalangeal syndrome type I or III

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014112.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPS1	NM_014112.5	MANE Select	c.-122+11003G>A		intron	N/A	NP_054831.2	Q9UHF7-2
	TRPS1	NM_001282903.3		c.-129+11003G>A		intron	N/A	NP_001269832.1
	TRPS1	NM_001282902.3		c.10+10332G>A		intron	N/A	NP_001269831.1	Q9UHF7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPS1	ENST00000395715.8	TSL:1 MANE Select	c.-122+11003G>A		intron	N/A	ENSP00000379065.3	Q9UHF7-2
	TRPS1	ENST00000220888.9	TSL:1	c.-3+11003G>A		intron	N/A	ENSP00000220888.5	Q9UHF7-1
	TRPS1	ENST00000519674.1	TSL:1	c.-3+11003G>A		intron	N/A	ENSP00000429174.1	E5RJ97

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69332 AN: 151694 Hom.: 17888 Cov.: 32

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.395

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.457 AC: 69422 AN: 151814 Hom.: 17920 Cov.: 32 AF XY: 0.462 AC XY: 34240 AN XY: 74186

African (AFR) AF: 0.698 AC: 28905 AN: 41418

American (AMR) AF: 0.481 AC: 7327 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 865 AN: 3472

East Asian (EAS) AF: 0.367 AC: 1888 AN: 5144

South Asian (SAS) AF: 0.382 AC: 1840 AN: 4822

European-Finnish (FIN) AF: 0.459 AC: 4819 AN: 10504

Middle Eastern (MID) AF: 0.264 AC: 77 AN: 292

European-Non Finnish (NFE) AF: 0.331 AC: 22457 AN: 67898

Other (OTH) AF: 0.397 AC: 837 AN: 2108

Alfa AF: 0.402 Hom.: 4845

Bravo AF: 0.471

Asia WGS AF: 0.418 AC: 1459 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.3
DANN	Benign	0.52
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs179442; hg19: chr8-116669769;