8-115412179-TA-T

Position:

• chr8-115412179-TA-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_014112.5(TRPS1):​c.*1843del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0442 in 145,368 control chromosomes in the GnomAD database, including 381 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.044 (381 hom., cov: 32)
  • Exomes 𝑓: 0.011 (0 hom.)
• Consequence: TRPS1 NM_014112.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.600

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 Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPS1	NM_014112.5	c.*1843del		3_prime_UTR_variant	7/7	ENST00000395715.8
TRPS1	NM_001282902.3	c.*1843del		3_prime_UTR_variant	6/6
TRPS1	NM_001282903.3	c.*1843del		3_prime_UTR_variant	7/7
TRPS1	NM_001330599.2	c.*1843del		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPS1	ENST00000395715.8	c.*1843del		3_prime_UTR_variant	7/7	1	NM_014112.5	A1
TRPS1	ENST00000640765.1	c.*1843del		3_prime_UTR_variant	6/6	2		P4

Frequencies

GnomAD3 genomes AF: 0.0442 AC: 6408 AN: 144942 Hom.: 380 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.0299

Gnomad AMR AF: 0.0160

Gnomad ASJ AF: 0.000883

Gnomad EAS AF: 0.00279

Gnomad SAS AF: 0.00477

Gnomad FIN AF: 0.00778

Gnomad MID AF: 0.0230

Gnomad NFE AF: 0.00443

Gnomad OTH AF: 0.0237

GnomAD4 exome AF: 0.0110 AC: 4 AN: 364 Hom.: 0 Cov.: 0 AF XY: 0.0133 AC XY: 3 AN XY: 226

Gnomad4 FIN exome AF: 0.0112

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0443 AC: 6422 AN: 145004 Hom.: 381 Cov.: 32 AF XY: 0.0424 AC XY: 2984 AN XY: 70446

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.0160

Gnomad4 ASJ AF: 0.000883

Gnomad4 EAS AF: 0.00279

Gnomad4 SAS AF: 0.00435

Gnomad4 FIN AF: 0.00778

Gnomad4 NFE AF: 0.00443

Gnomad4 OTH AF: 0.0260

Bravo AF: 0.0465

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Trichorhinophalangeal syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs886062619; hg19: chr8-116424407;