Variant 13-113325668-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_024719.4(GRTP1):c.914T>C(p.Phe305Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,850 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: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GRTP1
NM_024719.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.38

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.924

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GRTP1	NM_024719.4 linkuse as main transcript	c.914T>C	p.Phe305Ser	missense_variant	7/8	ENST00000375431.9
GRTP1	NM_001286732.2 linkuse as main transcript	c.914T>C	p.Phe305Ser	missense_variant	7/7
GRTP1	NM_001411029.1 linkuse as main transcript	c.680T>C	p.Phe227Ser	missense_variant	7/7
GRTP1	NM_001286733.1 linkuse as main transcript	c.563-1091T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRTP1	ENST00000375431.9 linkuse as main transcript	c.914T>C	p.Phe305Ser	missense_variant	7/8	1	NM_024719.4	P1	Q5TC63-1
GRTP1	ENST00000375430.8 linkuse as main transcript	c.914T>C	p.Phe305Ser	missense_variant	7/7	1			Q5TC63-3
GRTP1	ENST00000326039.3 linkuse as main transcript	c.680T>C	p.Phe227Ser	missense_variant	5/5	1			Q5TC63-2
GRTP1	ENST00000620217.4 linkuse as main transcript	c.563-1091T>C		intron_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251418

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

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:

1461850

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 22, 2023

The c.914T>C (p.F305S) alteration is located in exon 7 (coding exon 7) of the GRTP1 gene. This alteration results from a T to C substitution at nucleotide position 914, causing the phenylalanine (F) at amino acid position 305 to be replaced by a serine (S). 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

0.96

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Pathogenic

0.18

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

T;.;.

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.95

D;T;T

M_CAP

Uncertain

0.087

MetaRNN

Pathogenic

0.92

D;D;D

MetaSVM

Benign

-0.65

MutationAssessor

Pathogenic

3.2

M;M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.60

PROVEAN

Pathogenic

-7.7

D;D;D

REVEL

Uncertain

0.63

Sift

Pathogenic

0.0

D;D;D

Sift4G

Uncertain

0.0050

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.95

MutPred

0.68

Gain of catalytic residue at M300 (P = 0);Gain of catalytic residue at M300 (P = 0);.;

MVP

0.54

MPC

0.72

ClinPred

1.0

GERP RS

5.0

Varity_R

0.93

gMVP

0.78

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