8-115411268-CTAT-C

Variant names:

• chr8-115411268-CTAT-C
• rs886062612
• NM_014112.5:c.*2752_*2754delATA

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The NM_014112.5(TRPS1):​c.*2752_*2754delATA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000086 in 151,244 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.000086 (0 hom., cov: 32)
• Consequence: TRPS1 NM_014112.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.583
• Publications: 0 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: Likely_benign. The variant received -5 ACMG points.

• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000086 (13/151244) while in subpopulation AMR AF = 0.000725 (11/15170). AF 95% confidence interval is 0.000406. There are 0 homozygotes in GnomAd4. There are 7 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High AC in GnomAd4 at 13 AD gene.

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.*2752_*2754delATA		3_prime_UTR	Exon 7 of 7	NP_054831.2	Q9UHF7-2
	TRPS1	NM_001282903.3		c.*2752_*2754delATA		3_prime_UTR	Exon 7 of 7	NP_001269832.1
	TRPS1	NM_001282902.3		c.*2752_*2754delATA		3_prime_UTR	Exon 6 of 6	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.*2752_*2754delATA		3_prime_UTR	Exon 7 of 7	ENSP00000379065.3	Q9UHF7-2
	TRPS1	ENST00000640765.1	TSL:2	c.*2752_*2754delATA		3_prime_UTR	Exon 6 of 6	ENSP00000492037.1	Q9UHF7-1

Frequencies

GnomAD3 genomes AF: 0.0000860 AC: 13 AN: 151244 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000725

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000860 AC: 13 AN: 151244 Hom.: 0 Cov.: 32 AF XY: 0.0000949 AC XY: 7 AN XY: 73796

African (AFR) AF: 0.00 AC: 0 AN: 41162

American (AMR) AF: 0.000725 AC: 11 AN: 15170

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10348

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67838

Other (OTH) AF: 0.00 AC: 0 AN: 2072

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000110

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Trichorhinophalangeal syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs886062612; hg19: chr8-116423496;