Variant 13-113326041-C-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.613G>C(p.Gly205Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000253 in 1,460,916 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

GRTP1
NM_024719.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.17

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.613G>C	p.Gly205Arg	missense_variant	6/8	ENST00000375431.9	NP_078995.2
GRTP1	NM_001286732.2 linkuse as main transcript	c.613G>C	p.Gly205Arg	missense_variant	6/7		NP_001273661.1
GRTP1	NM_001411029.1 linkuse as main transcript	c.379G>C	p.Gly127Arg	missense_variant	6/7		NP_001397958.1
GRTP1	NM_001286733.1 linkuse as main transcript	c.563-1464G>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.613G>C	p.Gly205Arg	missense_variant	6/8	1	NM_024719.4	ENSP00000364580	P1	Q5TC63-1
GRTP1	ENST00000375430.8 linkuse as main transcript	c.613G>C	p.Gly205Arg	missense_variant	6/7	1		ENSP00000364579		Q5TC63-3
GRTP1	ENST00000326039.3 linkuse as main transcript	c.379G>C	p.Gly127Arg	missense_variant	4/5	1		ENSP00000321850		Q5TC63-2
GRTP1	ENST00000620217.4 linkuse as main transcript	c.563-1464G>C		intron_variant		2		ENSP00000483734

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000560

AC:

AN:

249802

Hom.:

AF XY:

0.0000887

AC XY:

AN XY:

135270

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:

0.000458

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000253

AC:

AN:

1460916

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

726806

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000383

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000494

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Feb 17, 2022

The c.613G>C (p.G205R) alteration is located in exon 6 (coding exon 6) of the GRTP1 gene. This alteration results from a G to C substitution at nucleotide position 613, causing the glycine (G) at amino acid position 205 to be replaced by an arginine (R). 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

0.38

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.044

T;.;.

Eigen

Benign

0.032

Eigen_PC

Benign

0.066

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.97

D;D;D

M_CAP

Benign

0.025

MetaRNN

Uncertain

0.68

D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.57

N;N;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-4.1

D;D;D

REVEL

Benign

0.28

Sift

Benign

0.40

T;T;T

Sift4G

Benign

0.50

T;T;T

Polyphen

0.99

D;.;B

Vest4

0.74

MutPred

0.49

Loss of disorder (P = 0.2844);Loss of disorder (P = 0.2844);.;

MVP

0.35

MPC

0.55

ClinPred

0.56

GERP RS

4.8

Varity_R

0.40

gMVP

0.83

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