chr10-992549-C-T

Variant summary

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

The NM_012341.3(GTPBP4):​c.109C>T​(p.His37Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H37D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

GTPBP4
NM_012341.3 missense

Scores

5
9
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.62
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GTPBP4NM_012341.3 linkc.109C>T p.His37Tyr missense_variant Exon 2 of 17 ENST00000360803.9 NP_036473.2 Q9BZE4-1D2CFK9
GTPBP4XM_047424932.1 linkc.-33C>T 5_prime_UTR_variant Exon 2 of 17 XP_047280888.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GTPBP4ENST00000360803.9 linkc.109C>T p.His37Tyr missense_variant Exon 2 of 17 1 NM_012341.3 ENSP00000354040.4 Q9BZE4-1
GTPBP4ENST00000360059 linkc.-33C>T 5_prime_UTR_variant Exon 2 of 5 5 ENSP00000353168.5 Q5T3R7
GTPBP4ENST00000491635.1 linkn.127C>T non_coding_transcript_exon_variant Exon 2 of 11 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
27
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.38
BayesDel_addAF
Uncertain
0.099
D
BayesDel_noAF
Benign
-0.10
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.19
T
Eigen
Pathogenic
0.74
Eigen_PC
Pathogenic
0.76
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.99
D
M_CAP
Benign
0.019
T
MetaRNN
Uncertain
0.60
D
MetaSVM
Benign
-0.94
T
MutationAssessor
Uncertain
2.6
M
PrimateAI
Pathogenic
0.93
D
PROVEAN
Uncertain
-3.3
D
REVEL
Uncertain
0.29
Sift
Uncertain
0.0060
D
Sift4G
Uncertain
0.024
D
Polyphen
0.99
D
Vest4
0.71
MutPred
0.45
Loss of disorder (P = 0.0655);
MVP
0.30
MPC
0.40
ClinPred
0.98
D
GERP RS
5.7
Varity_R
0.55
gMVP
0.69

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.

Other links and lift over

dbSNP: rs1206971152; hg19: chr10-1038489; API