rs796052183

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6

The ENST00000281543.6(GUF1):​c.655G>T​(p.Asp219Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000705 in 1,419,278 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

GUF1
ENST00000281543.6 missense

Scores

9
10

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.77
Variant links:
Genes affected
GUF1 (HGNC:25799): (GTP binding elongation factor GUF1) This gene encodes a GTPase that triggers back-translocation of the elongating ribosome during mitochondrial protein synthesis. The protein contains a highly conserved C-terminal domain not found in other GTPases that facilitates tRNA binding. The encoded protein is thought to prevent misincorporation of amino acids in stressful, suboptimal conditions. An allelic variant in this gene has been associated with early infantile epileptic encephalopathy-40. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]
GNPDA2 (HGNC:21526): (glucosamine-6-phosphate deaminase 2) The protein encoded by this gene is an allosteric enzyme that catalyzes the reversible reaction converting D-glucosamine-6-phosphate into D-fructose-6-phosphate and ammonium. Variations of this gene have been reported to be associated with influencing body mass index and susceptibility to obesity. A pseudogene of this gene is located on chromosome 9. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Aug 2012]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 4-44683304-G-T is Benign according to our data. Variant chr4-44683304-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 207915.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GUF1NM_021927.3 linkuse as main transcriptc.655G>T p.Asp219Tyr missense_variant 6/17 ENST00000281543.6 NP_068746.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GUF1ENST00000281543.6 linkuse as main transcriptc.655G>T p.Asp219Tyr missense_variant 6/171 NM_021927.3 ENSP00000281543 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.05e-7
AC:
1
AN:
1419278
Hom.:
0
Cov.:
26
AF XY:
0.00000141
AC XY:
1
AN XY:
707028
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000262
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.:
32

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Long QT syndrome Benign:1
Likely benign, no assertion criteria providedresearchMedical Research Institute, Tokyo Medical and Dental University-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.039
T
BayesDel_noAF
Benign
-0.29
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.36
T
Eigen
Uncertain
0.25
Eigen_PC
Benign
0.13
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Uncertain
0.94
D
M_CAP
Benign
0.027
D
MetaRNN
Uncertain
0.55
D
MetaSVM
Benign
-0.50
T
MutationAssessor
Uncertain
2.0
M
MutationTaster
Benign
0.99
N
PrimateAI
Benign
0.38
T
PROVEAN
Uncertain
-4.3
D
REVEL
Benign
0.29
Sift
Uncertain
0.0060
D
Sift4G
Uncertain
0.0050
D
Polyphen
0.85
P
Vest4
0.49
MutPred
0.45
Loss of solvent accessibility (P = 0.0807);
MVP
0.80
MPC
0.33
ClinPred
0.97
D
GERP RS
1.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.23
gMVP
0.52

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: rs796052183; hg19: chr4-44685321; API