NM_014112.5:c.-122+10344T>C

Variant names:

• chr8-115658201-A-G
• rs7828416
• NM_014112.5:c.-122+10344T>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+10344T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,000 control chromosomes in the GnomAD database, including 5,385 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 0.15 (5385 hom., cov: 32)
• Consequence: TRPS1 NM_014112.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.150
• Publications: 2 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPS1	NM_014112.5	c.-122+10344T>C		intron_variant	Intron 1 of 6	ENST00000395715.8	NP_054831.2
TRPS1	NM_001282903.3	c.-129+10344T>C		intron_variant	Intron 1 of 6		NP_001269832.1
TRPS1	NM_001282902.3	c.10+9673T>C		intron_variant	Intron 1 of 5		NP_001269831.1
TRPS1	NM_001330599.2	c.-3+10344T>C		intron_variant	Intron 1 of 5		NP_001317528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPS1	ENST00000395715.8	c.-122+10344T>C		intron_variant	Intron 1 of 6	1	NM_014112.5	ENSP00000379065.3

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22829 AN: 151882 Hom.: 5368 Cov.: 32

Gnomad AFR AF: 0.504

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0745

Gnomad ASJ AF: 0.00807

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0593

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.00519

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.151 AC: 22890 AN: 152000 Hom.: 5385 Cov.: 32 AF XY: 0.146 AC XY: 10881 AN XY: 74330

African (AFR) AF: 0.503 AC: 20823 AN: 41360

American (AMR) AF: 0.0743 AC: 1134 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00807 AC: 28 AN: 3470

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5170

South Asian (SAS) AF: 0.0587 AC: 283 AN: 4818

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10624

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.00519 AC: 353 AN: 67984

Other (OTH) AF: 0.115 AC: 243 AN: 2110

Alfa AF: 0.0609 Hom.: 5187

Bravo AF: 0.170

Asia WGS AF: 0.0720 AC: 252 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.6
DANN	Benign	0.51
PhyloP100		0.15
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: rs7828416; hg19: chr8-116670428;