Variant 13-113324531-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_024719.4(GRTP1):c.968A>G(p.Lys323Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GRTP1
NM_024719.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.99

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 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=0.12648192).

BP6

Variant 13-113324531-T-C is Benign according to our data. Variant chr13-113324531-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2617271.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GRTP1	NM_024719.4 linkuse as main transcript	c.968A>G	p.Lys323Arg	missense_variant	8/8	ENST00000375431.9	NP_078995.2
GRTP1	NM_001286733.1 linkuse as main transcript	c.609A>G	p.Gln203=	synonymous_variant	6/6		NP_001273662.1
GRTP1	NM_001411029.1 linkuse as main transcript	c.*1016A>G		3_prime_UTR_variant	7/7		NP_001397958.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRTP1	ENST00000375431.9 linkuse as main transcript	c.968A>G	p.Lys323Arg	missense_variant	8/8	1	NM_024719.4	ENSP00000364580	P1	Q5TC63-1
GRTP1	ENST00000620217.4 linkuse as main transcript	c.609A>G	p.Gln203=	synonymous_variant	6/6	2		ENSP00000483734

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000822

AC:

AN:

243200

Hom.:

AF XY:

0.00000756

AC XY:

AN XY:

132280

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000112

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:

0.00000137

AC:

AN:

1459708

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725984

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 08, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.0048

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.81

M_CAP

Benign

0.0083

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.51

MutationTaster

Benign

0.93

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.7

REVEL

Benign

0.052

Sift

Benign

0.28

Sift4G

Benign

0.16

Polyphen

0.11

Vest4

0.10

MutPred

0.30

Gain of catalytic residue at V321 (P = 0.0316);

MVP

0.22

MPC

0.097

ClinPred

0.46

GERP RS

-3.4

Varity_R

0.059

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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