Variant chr13-113325968-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_024719.4(GRTP1):c.686T>A(p.Leu229Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

GRTP1
NM_024719.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.47

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.814

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GRTP1	NM_024719.4 linkuse as main transcript	c.686T>A	p.Leu229Gln	missense_variant	6/8	ENST00000375431.9
GRTP1	NM_001286732.2 linkuse as main transcript	c.686T>A	p.Leu229Gln	missense_variant	6/7
GRTP1	NM_001411029.1 linkuse as main transcript	c.452T>A	p.Leu151Gln	missense_variant	6/7
GRTP1	NM_001286733.1 linkuse as main transcript	c.563-1391T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRTP1	ENST00000375431.9 linkuse as main transcript	c.686T>A	p.Leu229Gln	missense_variant	6/8	1	NM_024719.4	P1	Q5TC63-1
GRTP1	ENST00000375430.8 linkuse as main transcript	c.686T>A	p.Leu229Gln	missense_variant	6/7	1			Q5TC63-3
GRTP1	ENST00000326039.3 linkuse as main transcript	c.452T>A	p.Leu151Gln	missense_variant	4/5	1			Q5TC63-2
GRTP1	ENST00000620217.4 linkuse as main transcript	c.563-1391T>A		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152010

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

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461748

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727194

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:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152010

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74244

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

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

Mar 27, 2023

The c.686T>A (p.L229Q) alteration is located in exon 6 (coding exon 6) of the GRTP1 gene. This alteration results from a T to A substitution at nucleotide position 686, causing the leucine (L) at amino acid position 229 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

Pathogenic

0.66

BayesDel_addAF

Uncertain

0.051

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

T;.;.

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Benign

0.031

MetaRNN

Pathogenic

0.81

D;D;D

MetaSVM

Benign

-0.76

MutationAssessor

Uncertain

2.4

M;M;.

MutationTaster

Benign

0.81

D;D;D

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-3.5

D;D;D

REVEL

Benign

0.23

Sift

Uncertain

0.0040

D;D;D

Sift4G

Uncertain

0.0050

D;D;D

Polyphen

0.95

P;.;D

Vest4

0.79

MutPred

0.53

Gain of catalytic residue at V224 (P = 8e-04);Gain of catalytic residue at V224 (P = 8e-04);.;

MVP

0.54

MPC

0.45

ClinPred

0.97

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.53

gMVP

0.78

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