Variant 13-113325767-T-G 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.815A>C(p.Gln272Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000062 in 1,614,068 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

GRTP1
NM_024719.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.51

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 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.815A>C	p.Gln272Pro	missense_variant	7/8	ENST00000375431.9	NP_078995.2
GRTP1	NM_001286732.2 linkuse as main transcript	c.815A>C	p.Gln272Pro	missense_variant	7/7		NP_001273661.1
GRTP1	NM_001411029.1 linkuse as main transcript	c.581A>C	p.Gln194Pro	missense_variant	7/7		NP_001397958.1
GRTP1	NM_001286733.1 linkuse as main transcript	c.563-1190A>C		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.815A>C	p.Gln272Pro	missense_variant	7/8	1	NM_024719.4	ENSP00000364580	P1	Q5TC63-1
GRTP1	ENST00000375430.8 linkuse as main transcript	c.815A>C	p.Gln272Pro	missense_variant	7/7	1		ENSP00000364579		Q5TC63-3
GRTP1	ENST00000326039.3 linkuse as main transcript	c.581A>C	p.Gln194Pro	missense_variant	5/5	1		ENSP00000321850		Q5TC63-2
GRTP1	ENST00000620217.4 linkuse as main transcript	c.563-1190A>C		intron_variant		2		ENSP00000483734

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152182

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251448

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135898

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:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74338

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:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

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

Jan 23, 2024

The c.815A>C (p.Q272P) alteration is located in exon 7 (coding exon 7) of the GRTP1 gene. This alteration results from a A to C substitution at nucleotide position 815, causing the glutamine (Q) at amino acid position 272 to be replaced by a proline (P). 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

0.43

BayesDel_addAF

Benign

-0.022

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.051

T;.;.

Eigen

Benign

0.097

Eigen_PC

Benign

-0.044

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Benign

0.019

MetaRNN

Uncertain

0.70

D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

M;M;.

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-3.3

D;D;D

REVEL

Benign

0.22

Sift

Benign

0.14

T;T;T

Sift4G

Benign

0.19

T;T;T

Polyphen

0.99

D;.;.

Vest4

0.75

MutPred

0.48

Gain of catalytic residue at Q272 (P = 0.0041);Gain of catalytic residue at Q272 (P = 0.0041);.;

MVP

0.59

MPC

0.57

ClinPred

0.69

GERP RS

3.6

Varity_R

0.75

gMVP

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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