rs10505261

Variant names:

• chr8-115658439-A-G
• rs10505261
• NM_014112.5:c.-122+10106T>C

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+10106T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,116 control chromosomes in the GnomAD database, including 3,215 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 0.12 (3215 hom., cov: 32)
• Consequence: TRPS1 NM_014112.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.573
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.384 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+10106T>C		intron	N/A	NP_054831.2	Q9UHF7-2
	TRPS1	NM_001282903.3		c.-129+10106T>C		intron	N/A	NP_001269832.1
	TRPS1	NM_001282902.3		c.10+9435T>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.-122+10106T>C		intron	N/A	ENSP00000379065.3	Q9UHF7-2
	TRPS1	ENST00000220888.9	TSL:1	c.-3+10106T>C		intron	N/A	ENSP00000220888.5	Q9UHF7-1
	TRPS1	ENST00000519674.1	TSL:1	c.-3+10106T>C		intron	N/A	ENSP00000429174.1	E5RJ97

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17857 AN: 151998 Hom.: 3200 Cov.: 32

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0627

Gnomad ASJ AF: 0.00808

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0582

Gnomad FIN AF: 0.000470

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00479

Gnomad OTH AF: 0.0882

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

GnomAD4 genome AF: 0.118 AC: 17915 AN: 152116 Hom.: 3215 Cov.: 32 AF XY: 0.115 AC XY: 8585 AN XY: 74384

African (AFR) AF: 0.389 AC: 16103 AN: 41428

American (AMR) AF: 0.0625 AC: 956 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00808 AC: 28 AN: 3466

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5178

South Asian (SAS) AF: 0.0578 AC: 279 AN: 4826

European-Finnish (FIN) AF: 0.000470 AC: 5 AN: 10628

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.00479 AC: 326 AN: 67990

Other (OTH) AF: 0.0939 AC: 198 AN: 2108

Alfa AF: 0.0571 Hom.: 242

Bravo AF: 0.133

Asia WGS AF: 0.0680 AC: 238 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.3
DANN	Benign	0.46
PhyloP100		0.57
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: rs10505261; hg19: chr8-116670666;