Variant 1-3625157-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_182752.4(TPRG1L):c.85G>T(p.Gly29Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000129 in 1,238,518 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000037 ( 0 hom. )

Consequence

TPRG1L
NM_182752.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.760

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:

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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=0.099158615).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPRG1L	NM_182752.4 linkuse as main transcript	c.85G>T	p.Gly29Cys	missense_variant	1/5	ENST00000378344.7	NP_877429.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPRG1L	ENST00000378344.7 linkuse as main transcript	c.85G>T	p.Gly29Cys	missense_variant	1/5	2	NM_182752.4	ENSP00000367595	P1	Q5T0D9-1
TPRG1L	ENST00000344579.5 linkuse as main transcript	c.85G>T	p.Gly29Cys	missense_variant	1/4	1		ENSP00000339714		Q5T0D9-2

Frequencies

GnomAD3 genomes

AF:

0.0000793

AC:

AN:

151340

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:

0.00233

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:

0.00000368

AC:

AN:

1087070

Hom.:

Cov.:

AF XY:

0.00000194

AC XY:

AN XY:

514820

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000829

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000465

GnomAD4 genome

AF:

0.0000792

AC:

AN:

151448

Hom.:

Cov.:

AF XY:

0.0000811

AC XY:

AN XY:

73994

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00233

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000102

ExAC

AF:

0.000295

AC:

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 12, 2021

The c.85G>T (p.G29C) alteration is located in exon 1 (coding exon 1) of the TPRG1L gene. This alteration results from a G to T substitution at nucleotide position 85, causing the glycine (G) at amino acid position 29 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

Benign

0.15

BayesDel_addAF

Benign

-0.067

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.037

T;.

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.50

T;T

M_CAP

Uncertain

0.26

MetaRNN

Benign

0.099

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.95

N;N

REVEL

Benign

0.15

Sift

Benign

0.055

T;T

Sift4G

Uncertain

0.055

T;T

Polyphen

0.96

D;D

Vest4

0.20

MutPred

0.24

Loss of relative solvent accessibility (P = 0.0186);Loss of relative solvent accessibility (P = 0.0186);

MVP

0.31

MPC

0.29

ClinPred

0.23

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.21

gMVP

0.30

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