dbSNP rs770642820: TPRG1:p.Arg145His (chr3-189238864-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198485.4(TPRG1):c.434G>A(p.Arg145His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,613,328 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

TPRG1
NM_198485.4 missense

Scores

Clinical Significance

Not reported in ClinVar

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22623435).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPRG1	NM_198485.4 link	c.434G>A	p.Arg145His	missense_variant	Exon 4 of 6	ENST00000345063.8	NP_940887.1	Q6ZUI0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TPRG1	ENST00000345063.8 link	c.434G>A	p.Arg145His	missense_variant	Exon 4 of 6	1	NM_198485.4	ENSP00000341031.3	Q6ZUI0
TPRG1	ENST00000433971.5 link	c.434G>A	p.Arg145His	missense_variant	Exon 9 of 11	2		ENSP00000412547.1	Q6ZUI0
TPRG1	ENST00000425670.1 link	c.215G>A	p.Arg72His	missense_variant	Exon 2 of 4	3		ENSP00000400171.1	H7C1G4
TPRG1-AS2	ENST00000425454.1 link	n.301C>T		non_coding_transcript_exon_variant	Exon 3 of 3	5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000798

AC:

AN:

250496

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135332

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1461200

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

726898

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000944

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.023

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.053

T;T

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.65

.;T

M_CAP

Benign

0.0035

MetaRNN

Benign

0.23

T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

1.7

L;L

PrimateAI

Benign

0.27

PROVEAN

Benign

-2.0

N;N

REVEL

Benign

0.23

Sift

Benign

0.039

D;D

Sift4G

Benign

0.072

T;T

Polyphen

0.99

D;D

Vest4

0.32

MVP

0.030

MPC

0.034

ClinPred

0.66

GERP RS

4.8

Varity_R

0.088

gMVP

0.68

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over