Variant chr3-189238864-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_198485.4(TPRG1):c.434G>C(p.Arg145Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

TPRG1
NM_198485.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.18

Variant links:

Genes affected

TPRG1 (HGNC:24759): (tumor protein p63 regulated 1) Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TPRG1 links:

TPRG1-AS2 (HGNC:41062): (TPRG1 antisense RNA 2)

TPRG1-AS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31712365).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPRG1	NM_198485.4 linkuse as main transcript	c.434G>C	p.Arg145Pro	missense_variant	4/6	ENST00000345063.8
TPRG1-AS2	NR_046722.1 linkuse as main transcript	n.301C>G		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
TPRG1	ENST00000345063.8 linkuse as main transcript	c.434G>C	p.Arg145Pro	missense_variant	4/6	1	NM_198485.4	P1
TPRG1-AS2	ENST00000425454.1 linkuse as main transcript	n.301C>G		non_coding_transcript_exon_variant	3/3	5
TPRG1	ENST00000433971.5 linkuse as main transcript	c.434G>C	p.Arg145Pro	missense_variant	9/11	2		P1
TPRG1	ENST00000425670.1 linkuse as main transcript	c.218G>C	p.Arg73Pro	missense_variant	2/4	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1461200

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726898

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000900

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 08, 2023

The c.434G>C (p.R145P) alteration is located in exon 4 (coding exon 3) of the TPRG1 gene. This alteration results from a G to C substitution at nucleotide position 434, causing the arginine (R) at amino acid position 145 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.68

BayesDel_addAF

Uncertain

0.097

BayesDel_noAF

Benign

-0.10

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

T;T

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.072

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.69

.;T

M_CAP

Benign

0.0031

MetaRNN

Benign

0.32

T;T

MetaSVM

Benign

-0.83

MutationAssessor

Uncertain

2.4

M;M

MutationTaster

Benign

0.99

D;D

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-2.4

N;N

REVEL

Benign

0.15

Sift

Benign

0.043

D;D

Sift4G

Benign

0.071

T;T

Polyphen

0.0080

B;B

Vest4

0.64

MutPred

0.52

Gain of ubiquitination at K150 (P = 0.0467);Gain of ubiquitination at K150 (P = 0.0467);

MVP

0.072

MPC

0.040

ClinPred

0.93

GERP RS

4.8

Varity_R

0.60

gMVP

0.94

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over