Variant 10-1000772-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_012341.3(GTPBP4):c.750G>A(p.Ala250=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 1,607,090 control chromosomes in the GnomAD database, including 228,395 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 19788 hom., cov: 29)

Exomes 𝑓: 0.53 ( 208607 hom. )

Consequence

GTPBP4
NM_012341.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.31

Variant links:

Genes affected

GTPBP4 (HGNC:21535): (GTP binding protein 4) GTP-binding proteins are GTPases and function as molecular switches that can flip between two states: active, when GTP is bound, and inactive, when GDP is bound. 'Active' in this context usually means that the molecule acts as a signal to trigger other events in the cell. When an extracellular ligand binds to a G-protein-linked receptor, the receptor changes its conformation and switches on the trimeric G proteins that associate with it by causing them to eject their GDP and replace it with GTP. The switch is turned off when the G protein hydrolyzes its own bound GTP, converting it back to GDP. But before that occurs, the active protein has an opportunity to diffuse away from the receptor and deliver its message for a prolonged period to its downstream target. [provided by RefSeq, Jul 2008]

GTPBP4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 10-1000772-G-A is Benign according to our data. Variant chr10-1000772-G-A is described in ClinVar as [Benign]. Clinvar id is 1263198.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.31 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GTPBP4	NM_012341.3 linkuse as main transcript	c.750G>A	p.Ala250=	synonymous_variant	7/17	ENST00000360803.9
GTPBP4	XM_047424932.1 linkuse as main transcript	c.609G>A	p.Ala203=	synonymous_variant	7/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GTPBP4	ENST00000360803.9 linkuse as main transcript	c.750G>A	p.Ala250=	synonymous_variant	7/17	1	NM_012341.3	P1	Q9BZE4-1
GTPBP4	ENST00000491635.1 linkuse as main transcript	n.1629G>A		non_coding_transcript_exon_variant	5/11	2

Frequencies

GnomAD3 genomes

AF:

0.508

AC:

76912

AN:

151508

Hom.:

19761

Cov.:

show subpopulations

Gnomad AFR

AF:

0.432

Gnomad AMI

AF:

0.470

Gnomad AMR

AF:

0.523

Gnomad ASJ

AF:

0.457

Gnomad EAS

AF:

0.592

Gnomad SAS

AF:

0.605

Gnomad FIN

AF:

0.569

Gnomad MID

AF:

0.611

Gnomad NFE

AF:

0.530

Gnomad OTH

AF:

0.504

GnomAD3 exomes

AF:

0.534

AC:

131738

AN:

246514

Hom.:

35657

AF XY:

0.537

AC XY:

71474

AN XY:

133008

show subpopulations

Gnomad AFR exome

AF:

0.423

Gnomad AMR exome

AF:

0.545

Gnomad ASJ exome

AF:

0.444

Gnomad EAS exome

AF:

0.580

Gnomad SAS exome

AF:

0.595

Gnomad FIN exome

AF:

0.556

Gnomad NFE exome

AF:

0.528

Gnomad OTH exome

AF:

0.530

GnomAD4 exome

AF:

0.534

AC:

776926

AN:

1455462

Hom.:

208607

Cov.:

AF XY:

0.536

AC XY:

387946

AN XY:

723434

show subpopulations

Gnomad4 AFR exome

AF:

0.423

Gnomad4 AMR exome

AF:

0.547

Gnomad4 ASJ exome

AF:

0.449

Gnomad4 EAS exome

AF:

0.621

Gnomad4 SAS exome

AF:

0.595

Gnomad4 FIN exome

AF:

0.558

Gnomad4 NFE exome

AF:

0.530

Gnomad4 OTH exome

AF:

0.533

GnomAD4 genome

AF:

0.508

AC:

76970

AN:

151628

Hom.:

19788

Cov.:

AF XY:

0.512

AC XY:

37915

AN XY:

74076

show subpopulations

Gnomad4 AFR

AF:

0.432

Gnomad4 AMR

AF:

0.523

Gnomad4 ASJ

AF:

0.457

Gnomad4 EAS

AF:

0.593

Gnomad4 SAS

AF:

0.606

Gnomad4 FIN

AF:

0.569

Gnomad4 NFE

AF:

0.530

Gnomad4 OTH

AF:

0.510

Alfa

AF:

0.520

Hom.:

33020

Bravo

AF:

0.497

Asia WGS

AF:

0.604

AC:

2101

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.0050

DANN

Benign

0.35

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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