Variant 13-113325763-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024719.4(GRTP1):c.819C>A(p.His273Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000434 in 1,614,156 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000027 ( 1 hom. )

Consequence

GRTP1
NM_024719.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0550

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.051411867).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRTP1	NM_024719.4 link	c.819C>A	p.His273Gln	missense_variant	7/8	ENST00000375431.9	NP_078995.2	Q5TC63-1
GRTP1	NM_001286732.2 link	c.819C>A	p.His273Gln	missense_variant	7/7		NP_001273661.1	Q5TC63-3
GRTP1	NM_001411029.1 link	c.585C>A	p.His195Gln	missense_variant	7/7		NP_001397958.1
GRTP1	NM_001286733.1 link	c.563-1186C>A		intron_variant			NP_001273662.1	Q5TC63A0A087X0Y1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GRTP1	ENST00000375431.9 link	c.819C>A	p.His273Gln	missense_variant	7/8	1	NM_024719.4	ENSP00000364580.3	Q5TC63-1
GRTP1	ENST00000375430.8 link	c.819C>A	p.His273Gln	missense_variant	7/7	1		ENSP00000364579.4	Q5TC63-3
GRTP1	ENST00000326039.3 link	c.585C>A	p.His195Gln	missense_variant	5/5	1		ENSP00000321850.3	Q5TC63-2
GRTP1	ENST00000620217.4 link	c.563-1186C>A		intron_variant		2		ENSP00000483734.1	A0A087X0Y1

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

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

GnomAD3 exomes

AF:

0.0000915

AC:

AN:

251454

Hom.:

AF XY:

0.0000589

AC XY:

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.0000868

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000274

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.000896

Gnomad4 AMR exome

AF:

0.000157

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:

0.0000497

GnomAD4 genome

AF:

0.000197

AC:

AN:

152272

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.000722

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

Alfa

AF:

0.0000224

Hom.:

Bravo

AF:

0.000272

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000107

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

Sep 02, 2024

The c.819C>A (p.H273Q) alteration is located in exon 7 (coding exon 7) of the GRTP1 gene. This alteration results from a C to A substitution at nucleotide position 819, causing the histidine (H) at amino acid position 273 to be replaced by a glutamine (Q). 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

0.21

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.39

CADD

Benign

9.3

DANN

Benign

0.96

DEOGEN2

Benign

0.054

T;.;.

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.62

LIST_S2

Uncertain

0.86

D;D;D

M_CAP

Benign

0.016

MetaRNN

Benign

0.051

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Pathogenic

3.1

M;M;.

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-5.0

D;D;D

REVEL

Benign

0.20

Sift

Uncertain

0.023

D;D;D

Sift4G

Benign

0.066

T;D;T

Polyphen

0.99

D;.;.

Vest4

0.62

MutPred

0.49

Gain of catalytic residue at Q272 (P = 0.161);Gain of catalytic residue at Q272 (P = 0.161);.;

MVP

0.32

MPC

0.52

ClinPred

0.56

GERP RS

-2.0

Varity_R

0.36

gMVP

0.56

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