Variant chr13-113326029-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024719.4(GRTP1):c.625C>T(p.Arg209Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000397 in 1,613,170 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

GRTP1
NM_024719.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.87

Variant links:

Genes affected

GRTP1 (HGNC:20310): (growth hormone regulated TBC protein 1) Predicted to enable GTPase activator activity. Predicted to be involved in activation of GTPase activity and intracellular protein transport. [provided by Alliance of Genome Resources, Apr 2022]

GRTP1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GRTP1	NM_024719.4 linkuse as main transcript	c.625C>T	p.Arg209Trp	missense_variant	6/8	ENST00000375431.9	NP_078995.2
GRTP1	NM_001286732.2 linkuse as main transcript	c.625C>T	p.Arg209Trp	missense_variant	6/7		NP_001273661.1
GRTP1	NM_001411029.1 linkuse as main transcript	c.391C>T	p.Arg131Trp	missense_variant	6/7		NP_001397958.1
GRTP1	NM_001286733.1 linkuse as main transcript	c.563-1452C>T		intron_variant			NP_001273662.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRTP1	ENST00000375431.9 linkuse as main transcript	c.625C>T	p.Arg209Trp	missense_variant	6/8	1	NM_024719.4	ENSP00000364580	P1	Q5TC63-1
GRTP1	ENST00000375430.8 linkuse as main transcript	c.625C>T	p.Arg209Trp	missense_variant	6/7	1		ENSP00000364579		Q5TC63-3
GRTP1	ENST00000326039.3 linkuse as main transcript	c.391C>T	p.Arg131Trp	missense_variant	4/5	1		ENSP00000321850		Q5TC63-2
GRTP1	ENST00000620217.4 linkuse as main transcript	c.563-1452C>T		intron_variant		2		ENSP00000483734

Frequencies

GnomAD3 genomes

AF:

0.0000922

AC:

AN:

151826

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000218

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000559

AC:

AN:

250308

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135444

show subpopulations

Gnomad AFR exome

AF:

0.000309

Gnomad AMR exome

AF:

0.000202

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:

0.0000342

AC:

AN:

1461226

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

726944

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000112

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:

0.0000306

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.0000921

AC:

AN:

151944

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000442

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000155

Hom.:

Bravo

AF:

0.000155

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.0000545

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

Apr 01, 2024

The c.625C>T (p.R209W) alteration is located in exon 6 (coding exon 6) of the GRTP1 gene. This alteration results from a C to T substitution at nucleotide position 625, causing the arginine (R) at amino acid position 209 to be replaced by a tryptophan (W). 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

0.14

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

T;.;.

Eigen

Benign

-0.10

Eigen_PC

Benign

-0.37

FATHMM_MKL

Uncertain

0.79

LIST_S2

Pathogenic

0.98

D;D;D

M_CAP

Benign

0.071

MetaRNN

Uncertain

0.59

D;D;D

MetaSVM

Benign

-0.76

MutationAssessor

Pathogenic

3.1

M;M;.

MutationTaster

Benign

0.96

D;D;D

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-6.0

D;D;D

REVEL

Benign

0.24

Sift

Uncertain

0.0050

D;D;D

Sift4G

Uncertain

0.0040

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.63

MVP

0.38

MPC

0.56

ClinPred

0.97

GERP RS

-2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.31

gMVP

0.74

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