rs2142333

Variant names:

• chr8-115647231-C-T
• rs2142333
• NM_014112.5:c.-122+21314G>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+21314G>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 151,776 control chromosomes in the GnomAD database, including 17,876 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 (17876 hom., cov: 32)
• Consequence: TRPS1 NM_014112.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.139
• Publications: 5 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPS1	NM_014112.5	c.-122+21314G>A		intron_variant	Intron 1 of 6	ENST00000395715.8	NP_054831.2
TRPS1	NM_001282903.3	c.-129+21314G>A		intron_variant	Intron 1 of 6		NP_001269832.1
TRPS1	NM_001282902.3	c.10+20643G>A		intron_variant	Intron 1 of 5		NP_001269831.1
TRPS1	NM_001330599.2	c.-3+21314G>A		intron_variant	Intron 1 of 5		NP_001317528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPS1	ENST00000395715.8	c.-122+21314G>A		intron_variant	Intron 1 of 6	1	NM_014112.5	ENSP00000379065.3

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69324 AN: 151656 Hom.: 17846 Cov.: 32

Gnomad AFR AF: 0.694

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.276

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.457 AC: 69409 AN: 151776 Hom.: 17876 Cov.: 32 AF XY: 0.462 AC XY: 34253 AN XY: 74144

African (AFR) AF: 0.693 AC: 28705 AN: 41400

American (AMR) AF: 0.481 AC: 7338 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 940 AN: 3470

East Asian (EAS) AF: 0.368 AC: 1901 AN: 5168

South Asian (SAS) AF: 0.399 AC: 1919 AN: 4808

European-Finnish (FIN) AF: 0.461 AC: 4851 AN: 10520

Middle Eastern (MID) AF: 0.276 AC: 80 AN: 290

European-Non Finnish (NFE) AF: 0.331 AC: 22439 AN: 67832

Other (OTH) AF: 0.394 AC: 830 AN: 2108

Alfa AF: 0.401 Hom.: 1723

Bravo AF: 0.470

Asia WGS AF: 0.416 AC: 1447 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.7
DANN	Benign	0.45
PhyloP100		-0.14
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: rs2142333; hg19: chr8-116659458;