Genetic Variant NM_014112.5:c.*4315T>G (chr8-115409708-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014112.5(TRPS1):c.*4315T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 151,816 control chromosomes in the GnomAD database, including 26,844 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 0.58 ( 26840 hom., cov: 32)

Exomes 𝑓: 0.44 ( 4 hom. )

Consequence

TRPS1
NM_014112.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.161

Publications

13 publications found

Variant links:

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

TRPS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TRPS1	NM_014112.5 link	c.*4315T>G	3_prime_UTR_variant	Exon 7 of 7	ENST00000395715.8	NP_054831.2	Q9UHF7-2
TRPS1	NM_001282903.3 link	c.*4315T>G	3_prime_UTR_variant	Exon 7 of 7		NP_001269832.1	Q9UHF7
TRPS1	NM_001282902.3 link	c.*4315T>G	3_prime_UTR_variant	Exon 6 of 6		NP_001269831.1	Q9UHF7-3
TRPS1	NM_001330599.2 link	c.*4315T>G	3_prime_UTR_variant	Exon 6 of 6		NP_001317528.1	Q9UHF7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPS1	ENST00000395715.8 link	c.*4315T>G		3_prime_UTR_variant	Exon 7 of 7	1	NM_014112.5	ENSP00000379065.3		Q9UHF7-2
TRPS1	ENST00000640765.1 link	c.*4315T>G		3_prime_UTR_variant	Exon 6 of 6	2		ENSP00000492037.1		Q9UHF7-1

Frequencies

GnomAD3 genomes

AF:

0.579

AC:

87786

AN:

151664

Hom.:

26789

Cov.:

show subpopulations

Gnomad AFR

AF:

0.784

Gnomad AMI

AF:

0.574

Gnomad AMR

AF:

0.543

Gnomad ASJ

AF:

0.396

Gnomad EAS

AF:

0.574

Gnomad SAS

AF:

0.560

Gnomad FIN

AF:

0.416

Gnomad MID

AF:

0.380

Gnomad NFE

AF:

0.501

Gnomad OTH

AF:

0.524

GnomAD4 exome

AF:

0.438

AC:

AN:

Hom.:

Cov.:

AF XY:

0.455

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.423

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.579

AC:

87896

AN:

151784

Hom.:

26840

Cov.:

AF XY:

0.575

AC XY:

42608

AN XY:

74156

show subpopulations

African (AFR)

AF:

0.784

AC:

32491

AN:

41432

American (AMR)

AF:

0.543

AC:

8259

AN:

15214

Ashkenazi Jewish (ASJ)

AF:

0.396

AC:

1374

AN:

3466

East Asian (EAS)

AF:

0.575

AC:

2949

AN:

5132

South Asian (SAS)

AF:

0.560

AC:

2696

AN:

4810

European-Finnish (FIN)

AF:

0.416

AC:

4397

AN:

10558

Middle Eastern (MID)

AF:

0.391

AC:

115

AN:

294

European-Non Finnish (NFE)

AF:

0.501

AC:

33999

AN:

67864

Other (OTH)

AF:

0.520

AC:

1094

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1792

3584

5375

7167

8959

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

734

1468

2202

2936

3670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.524

Hom.:

94663

Bravo

AF:

0.597

Asia WGS

AF:

0.559

AC:

1943

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.2

(source)

DANN

Benign

0.64

PhyloP100

-0.16

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over