rs10505257

Variant names:

• chr8-115583081-G-A
• rs10505257
• NM_014112.5:c.2700+3920C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-115583081-G-A
• chr8-115583081-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014112.5(TRPS1):​c.2700+3920C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 151,956 control chromosomes in the GnomAD database, including 1,746 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 0.14 (1746 hom., cov: 32)
• Consequence: TRPS1 NM_014112.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.638
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPS1	NM_014112.5	c.2700+3920C>T		intron_variant	Intron 5 of 6	ENST00000395715.8	NP_054831.2
TRPS1	NM_001282903.3	c.2679+3920C>T		intron_variant	Intron 5 of 6		NP_001269832.1
TRPS1	NM_001282902.3	c.2673+3920C>T		intron_variant	Intron 4 of 5		NP_001269831.1
TRPS1	NM_001330599.2	c.2661+3920C>T		intron_variant	Intron 4 of 5		NP_001317528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPS1	ENST00000395715.8	c.2700+3920C>T		intron_variant	Intron 5 of 6	1	NM_014112.5	ENSP00000379065.3

Frequencies

GnomAD3 genomes AF: 0.138 AC: 21019 AN: 151840 Hom.: 1747 Cov.: 32

Gnomad AFR AF: 0.0661

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0500

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.138 AC: 21009 AN: 151956 Hom.: 1746 Cov.: 32 AF XY: 0.135 AC XY: 10024 AN XY: 74276

African (AFR) AF: 0.0659 AC: 2730 AN: 41444

American (AMR) AF: 0.140 AC: 2130 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 587 AN: 3472

East Asian (EAS) AF: 0.000773 AC: 4 AN: 5174

South Asian (SAS) AF: 0.0494 AC: 238 AN: 4820

European-Finnish (FIN) AF: 0.151 AC: 1591 AN: 10530

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13187 AN: 67952

Other (OTH) AF: 0.159 AC: 336 AN: 2110

Alfa AF: 0.145 Hom.: 1363

Bravo AF: 0.136

Asia WGS AF: 0.0250 AC: 87 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.57
DANN	Benign	0.70
PhyloP100		-0.64
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: rs10505257; hg19: chr8-116595308;