NM_014112.5:c.2700+10T>C

Variant names:

• chr8-115586991-A-G
• rs76046106
• NM_014112.5:c.2700+10T>C

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_014112.5(TRPS1):​c.2700+10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00589 in 1,614,004 control chromosomes in the GnomAD database, including 440 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.031 (231 hom., cov: 33)
  • Exomes 𝑓: 0.0032 (209 hom.)
• Consequence: TRPS1 NM_014112.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 2.88
• Publications: 1 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 8-115586991-A-G is Benign according to our data. Variant chr8-115586991-A-G is described in ClinVar as Benign. ClinVar VariationId is 260330.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPS1	NM_014112.5	MANE Select	c.2700+10T>C		intron	N/A	NP_054831.2
	TRPS1	NM_001282903.3		c.2679+10T>C		intron	N/A	NP_001269832.1
	TRPS1	NM_001282902.3		c.2673+10T>C		intron	N/A	NP_001269831.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPS1	ENST00000395715.8	TSL:1 MANE Select	c.2700+10T>C		intron	N/A	ENSP00000379065.3
	TRPS1	ENST00000220888.9	TSL:1	c.2661+10T>C		intron	N/A	ENSP00000220888.5
	TRPS1	ENST00000519674.1	TSL:1	c.2661+10T>C		intron	N/A	ENSP00000429174.1

Frequencies

GnomAD3 genomes AF: 0.0312 AC: 4751 AN: 152174 Hom.: 228 Cov.: 33

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0186

GnomAD2 exomes AF: 0.00821 AC: 2034 AN: 247730 AF XY: 0.00585

Gnomad AFR exome AF: 0.114

Gnomad AMR exome AF: 0.00690

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000241

Gnomad OTH exome AF: 0.00612

GnomAD4 exome AF: 0.00324 AC: 4730 AN: 1461712 Hom.: 209 Cov.: 34 AF XY: 0.00273 AC XY: 1986 AN XY: 727160

African (AFR) AF: 0.110 AC: 3687 AN: 33476

American (AMR) AF: 0.00798 AC: 357 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000336 AC: 29 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53302

Middle Eastern (MID) AF: 0.00592 AC: 34 AN: 5744

European-Non Finnish (NFE) AF: 0.000147 AC: 164 AN: 1111996

Other (OTH) AF: 0.00760 AC: 459 AN: 60386

GnomAD4 genome AF: 0.0314 AC: 4776 AN: 152292 Hom.: 231 Cov.: 33 AF XY: 0.0303 AC XY: 2258 AN XY: 74458

African (AFR) AF: 0.109 AC: 4532 AN: 41554

American (AMR) AF: 0.0118 AC: 180 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68022

Other (OTH) AF: 0.0184 AC: 39 AN: 2114

Alfa AF: 0.0157 Hom.: 35

Bravo AF: 0.0363

Asia WGS AF: 0.00664 AC: 23 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 24, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Trichorhinophalangeal dysplasia type I;C1860823:Trichorhinophalangeal syndrome, type III Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	16
DANN	Uncertain	1.0
PhyloP100		2.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs76046106; hg19: chr8-116599218; COSMIC: COSV55265354; COSMIC: COSV55265354;