Variant chr3-112991223-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_014170.4(GTPBP8):c.224C>T(p.Pro75Leu) 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 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GTPBP8
NM_014170.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.86

Variant links:

Genes affected

GTPBP8 (HGNC:25007): (GTP binding protein 8 (putative)) Predicted to enable GTP binding activity and metal ion binding activity. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

GTPBP8 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03820038).

BP6

Variant 3-112991223-C-T is Benign according to our data. Variant chr3-112991223-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2307852.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GTPBP8	NM_014170.4 linkuse as main transcript	c.224C>T	p.Pro75Leu	missense_variant	1/6	ENST00000383678.8	NP_054889.2	Q8N3Z3-1Q9P025
GTPBP8	NM_138485.2 linkuse as main transcript	c.224C>T	p.Pro75Leu	missense_variant	1/5		NP_612494.1	Q8N3Z3-2
GTPBP8	XM_047448046.1 linkuse as main transcript	c.224C>T	p.Pro75Leu	missense_variant	1/3		XP_047304002.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GTPBP8	ENST00000383678.8 linkuse as main transcript	c.224C>T	p.Pro75Leu	missense_variant	1/6	1	NM_014170.4	ENSP00000373176.2		Q8N3Z3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461838

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727220

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.:

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 17, 2022

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

0.062

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

5.1

DANN

Benign

0.88

DEOGEN2

Benign

0.0074

T;.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.63

T;.;T

M_CAP

Benign

0.0030

MetaRNN

Benign

0.038

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-1.7

N;N;.

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.54

N;N;.

REVEL

Benign

0.064

Sift

Benign

1.0

T;T;.

Sift4G

Benign

0.49

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.17

MutPred

0.58

Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);

MVP

0.048

MPC

0.11

ClinPred

0.060

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.029

gMVP

0.37

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over