Variant chr1-3625199-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_182752.4(TPRG1L):c.127C>T(p.Arg43Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000695 in 1,295,360 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: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 8.7e-7 ( 0 hom. )

Consequence

TPRG1L
NM_182752.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.10

Variant links:

Genes affected

TPRG1L (HGNC:27007): (tumor protein p63 regulated 1 like) Predicted to enable identical protein binding activity. Predicted to be involved in regulation of glutamatergic synaptic transmission. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

TPRG1L 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=0.3639614).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPRG1L	NM_182752.4 linkuse as main transcript	c.127C>T	p.Arg43Cys	missense_variant	1/5	ENST00000378344.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPRG1L	ENST00000378344.7 linkuse as main transcript	c.127C>T	p.Arg43Cys	missense_variant	1/5	2	NM_182752.4	P1	Q5T0D9-1
TPRG1L	ENST00000344579.5 linkuse as main transcript	c.127C>T	p.Arg43Cys	missense_variant	1/4	1			Q5T0D9-2

Frequencies

GnomAD3 genomes

AF:

0.0000528

AC:

AN:

151568

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

8.74e-7

AC:

AN:

1143792

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

547934

show subpopulations

Gnomad4 AFR exome

AF:

0.0000442

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000528

AC:

AN:

151568

Hom.:

Cov.:

AF XY:

0.0000540

AC XY:

AN XY:

74032

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000604

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

Jun 03, 2022

The c.127C>T (p.R43C) alteration is located in exon 1 (coding exon 1) of the TPRG1L gene. This alteration results from a C to T substitution at nucleotide position 127, causing the arginine (R) at amino acid position 43 to be replaced by a cysteine (C). 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

Uncertain

0.56

BayesDel_addAF

Benign

-0.0062

BayesDel_noAF

Benign

-0.25

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.061

T;.

Eigen

Benign

0.17

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.89

D;D

M_CAP

Pathogenic

0.82

MetaRNN

Benign

0.36

T;T

MetaSVM

Benign

-0.82

MutationAssessor

Benign

0.69

N;N

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.18

Sift

Uncertain

0.022

D;D

Sift4G

Uncertain

0.030

D;D

Polyphen

1.0

D;D

Vest4

0.19

MutPred

0.41

Loss of MoRF binding (P = 0.0102);Loss of MoRF binding (P = 0.0102);

MVP

0.28

MPC

1.1

ClinPred

0.92

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.29

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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