rs7823278

Variant names:

• chr8-115619675-C-A
• rs7823278
• NM_014112.5:c.423G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-115619675-C-A
• chr8-115619675-C-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_014112.5(TRPS1):​c.423G>T​(p.Pro141Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0282 in 1,614,012 control chromosomes in the GnomAD database, including 8,729 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (4548 hom., cov: 32)
  • Exomes 𝑓: 0.017 (4181 hom.)
• Consequence: TRPS1 NM_014112.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 3.41
• 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 8-115619675-C-A is Benign according to our data. Variant chr8-115619675-C-A is described in ClinVar as Benign. ClinVar VariationId is 260333.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=3.41 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.457 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.423G>T	p.Pro141Pro	synonymous	Exon 3 of 7	NP_054831.2	Q9UHF7-2
	TRPS1	NM_001282903.3		c.402G>T	p.Pro134Pro	synonymous	Exon 3 of 7	NP_001269832.1
	TRPS1	NM_001282902.3		c.396G>T	p.Pro132Pro	synonymous	Exon 2 of 6	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.423G>T	p.Pro141Pro	synonymous	Exon 3 of 7	ENSP00000379065.3	Q9UHF7-2
	TRPS1	ENST00000220888.9	TSL:1	c.384G>T	p.Pro128Pro	synonymous	Exon 2 of 6	ENSP00000220888.5	Q9UHF7-1
	TRPS1	ENST00000519674.1	TSL:1	c.384G>T	p.Pro128Pro	synonymous	Exon 2 of 5	ENSP00000429174.1	E5RJ97

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20542 AN: 152014 Hom.: 4537 Cov.: 32

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0539

Gnomad ASJ AF: 0.00433

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0468

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.00243

Gnomad OTH AF: 0.0881

GnomAD2 exomes AF: 0.0405 AC: 10096 AN: 249116 AF XY: 0.0339

Gnomad AFR exome AF: 0.473

Gnomad AMR exome AF: 0.0292

Gnomad ASJ exome AF: 0.00437

Gnomad EAS exome AF: 0.000223

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00214

Gnomad OTH exome AF: 0.0232

GnomAD4 exome AF: 0.0171 AC: 24938 AN: 1461880 Hom.: 4181 Cov.: 32 AF XY: 0.0163 AC XY: 11871 AN XY: 727242

African (AFR) AF: 0.475 AC: 15902 AN: 33480

American (AMR) AF: 0.0326 AC: 1458 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00524 AC: 137 AN: 26134

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39698

South Asian (SAS) AF: 0.0417 AC: 3598 AN: 86256

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53418

Middle Eastern (MID) AF: 0.0319 AC: 184 AN: 5768

European-Non Finnish (NFE) AF: 0.00127 AC: 1411 AN: 1112006

Other (OTH) AF: 0.0371 AC: 2240 AN: 60396

GnomAD4 genome AF: 0.135 AC: 20596 AN: 152132 Hom.: 4548 Cov.: 32 AF XY: 0.131 AC XY: 9760 AN XY: 74382

African (AFR) AF: 0.462 AC: 19166 AN: 41450

American (AMR) AF: 0.0538 AC: 823 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00433 AC: 15 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.0464 AC: 224 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.00243 AC: 165 AN: 68006

Other (OTH) AF: 0.0872 AC: 184 AN: 2110

Alfa AF: 0.0504 Hom.: 2576

Bravo AF: 0.152

Asia WGS AF: 0.0520 AC: 180 AN: 3478

EpiCase AF: 0.00284

EpiControl AF: 0.00231

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)
-	-	1	Trichorhinophalangeal dysplasia type I;C1860823:Trichorhinophalangeal syndrome, type III (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	10
DANN	Benign	0.69
PhyloP100		3.4
PromoterAI		-0.0065	Neutral
Mutation Taster		=98/2	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: rs7823278; hg19: chr8-116631902;