4-44685384-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021927.3(GUF1):​c.670-575A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.746 in 151,972 control chromosomes in the GnomAD database, including 42,672 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.75 ( 42672 hom., cov: 32)

Consequence

GUF1
NM_021927.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.752
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 Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.97).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GUF1NM_021927.3 linkc.670-575A>G intron_variant ENST00000281543.6 NP_068746.2 Q8N442

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GUF1ENST00000281543.6 linkc.670-575A>G intron_variant 1 NM_021927.3 ENSP00000281543.5 Q8N442

Frequencies

GnomAD3 genomes
AF:
0.746
AC:
113269
AN:
151854
Hom.:
42641
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.662
Gnomad AMI
AF:
0.806
Gnomad AMR
AF:
0.814
Gnomad ASJ
AF:
0.737
Gnomad EAS
AF:
0.775
Gnomad SAS
AF:
0.662
Gnomad FIN
AF:
0.845
Gnomad MID
AF:
0.652
Gnomad NFE
AF:
0.770
Gnomad OTH
AF:
0.743
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.746
AC:
113356
AN:
151972
Hom.:
42672
Cov.:
32
AF XY:
0.750
AC XY:
55719
AN XY:
74280
show subpopulations
Gnomad4 AFR
AF:
0.662
Gnomad4 AMR
AF:
0.814
Gnomad4 ASJ
AF:
0.737
Gnomad4 EAS
AF:
0.775
Gnomad4 SAS
AF:
0.661
Gnomad4 FIN
AF:
0.845
Gnomad4 NFE
AF:
0.770
Gnomad4 OTH
AF:
0.744
Alfa
AF:
0.767
Hom.:
59093
Bravo
AF:
0.746
Asia WGS
AF:
0.768
AC:
2674
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.97
CADD
Benign
1.6
DANN
Benign
0.74

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: rs12499960; hg19: chr4-44687401; API