3-112991094-C-T

Position:

• chr3-112991094-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014170.4(GTPBP8):​c.95C>T​(p.Ala32Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GTPBP8 NM_014170.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0810

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]

ENSG00000272844 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18215057).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GTPBP8	NM_014170.4	c.95C>T	p.Ala32Val	missense_variant	1/6	ENST00000383678.8	NP_054889.2
GTPBP8	NM_138485.2	c.95C>T	p.Ala32Val	missense_variant	1/5		NP_612494.1
GTPBP8	XM_047448046.1	c.95C>T	p.Ala32Val	missense_variant	1/3		XP_047304002.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GTPBP8	ENST00000383678.8	c.95C>T	p.Ala32Val	missense_variant	1/6	1	NM_014170.4	ENSP00000373176.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 08, 2024

The c.95C>T (p.A32V) alteration is located in exon 1 (coding exon 1) of the GTPBP8 gene. This alteration results from a C to T substitution at nucleotide position 95, causing the alanine (A) at amino acid position 32 to be replaced by a valine (V). 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	Benign	0.11
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0097	T;.;T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.83	T;.;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.3	M;M;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.81	N;N;.
REVEL	Benign	0.089
Sift	Uncertain	0.0070	D;D;.
Sift4G	Uncertain	0.010	D;D;D
Polyphen		0.48	P;P;.
Vest4		0.13
MutPred		0.66		Gain of glycosylation at S28 (P = 0.0448);Gain of glycosylation at S28 (P = 0.0448);Gain of glycosylation at S28 (P = 0.0448);
MVP		0.22
MPC		0.11
ClinPred		0.44	T
GERP RS		3.4
Varity_R		0.10
gMVP		0.54

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.

Other links and lift over

hg19: chr3-112709941;