8-115415107-A-G

Variant names:

• chr8-115415107-A-G
• rs752405769
• NM_014112.5:c.2824-23T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Moderate BS2

The NM_014112.5(TRPS1):​c.2824-23T>C variant causes a intron change. The variant allele was found at a frequency of 0.0000035 in 1,427,076 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: TRPS1 NM_014112.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.53
• 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BS2: High AC in GnomAdExome4 at 5 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.2824-23T>C		intron	N/A	NP_054831.2	Q9UHF7-2
	TRPS1	NM_001282903.3		c.2803-23T>C		intron	N/A	NP_001269832.1
	TRPS1	NM_001282902.3		c.2797-23T>C		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.2824-23T>C		intron	N/A	ENSP00000379065.3	Q9UHF7-2
	TRPS1	ENST00000220888.9	TSL:1	c.2785-23T>C		intron	N/A	ENSP00000220888.5	Q9UHF7-1
	TRPS1	ENST00000917131.1		c.2824-23T>C		intron	N/A	ENSP00000587190.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000469 AC: 1 AN: 213164 AF XY: 0.00000858

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000988

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000350 AC: 5 AN: 1427076 Hom.: 0 Cov.: 28 AF XY: 0.00000563 AC XY: 4 AN XY: 710074

African (AFR) AF: 0.00 AC: 0 AN: 31206

American (AMR) AF: 0.00 AC: 0 AN: 34392

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24078

East Asian (EAS) AF: 0.00 AC: 0 AN: 39534

South Asian (SAS) AF: 0.0000373 AC: 3 AN: 80476

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5568

European-Non Finnish (NFE) AF: 9.09e-7 AC: 1 AN: 1100440

Other (OTH) AF: 0.0000170 AC: 1 AN: 58786

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	20
DANN	Benign	0.89
PhyloP100		5.5

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs752405769; hg19: chr8-116427335;