Variant 4-44682421-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_021927.3(GUF1):c.585+10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0656 in 1,427,232 control chromosomes in the GnomAD database, including 3,626 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.077 ( 539 hom., cov: 32)

Exomes 𝑓: 0.064 ( 3087 hom. )

Consequence

GUF1
NM_021927.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0920

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]

GUF1 links:

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]

GNPDA2 links:

GUF1 (HGNC:):

GUF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 4-44682421-A-G is Benign according to our data. Variant chr4-44682421-A-G is described in ClinVar as [Benign]. Clinvar id is 1633236.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GUF1	NM_021927.3 linkuse as main transcript	c.585+10A>G		intron_variant		ENST00000281543.6	NP_068746.2	Q8N442

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GUF1	ENST00000281543.6 linkuse as main transcript	c.585+10A>G		intron_variant		1	NM_021927.3	ENSP00000281543.5		Q8N442

Frequencies

GnomAD3 genomes

AF:

0.0773

AC:

11758

AN:

152072

Hom.:

539

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0896

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.132

Gnomad ASJ

AF:

0.0432

Gnomad EAS

AF:

0.124

Gnomad SAS

AF:

0.0534

Gnomad FIN

AF:

0.0712

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0596

Gnomad OTH

AF:

0.0698

GnomAD3 exomes

AF:

0.0775

AC:

13072

AN:

168678

Hom.:

689

AF XY:

0.0720

AC XY:

6578

AN XY:

91424

show subpopulations

Gnomad AFR exome

AF:

0.0871

Gnomad AMR exome

AF:

0.183

Gnomad ASJ exome

AF:

0.0357

Gnomad EAS exome

AF:

0.106

Gnomad SAS exome

AF:

0.0546

Gnomad FIN exome

AF:

0.0756

Gnomad NFE exome

AF:

0.0593

Gnomad OTH exome

AF:

0.0743

GnomAD4 exome

AF:

0.0642

AC:

81841

AN:

1275042

Hom.:

3087

Cov.:

AF XY:

0.0630

AC XY:

39960

AN XY:

634118

show subpopulations

Gnomad4 AFR exome

AF:

0.0882

Gnomad4 AMR exome

AF:

0.163

Gnomad4 ASJ exome

AF:

0.0411

Gnomad4 EAS exome

AF:

0.135

Gnomad4 SAS exome

AF:

0.0487

Gnomad4 FIN exome

AF:

0.0776

Gnomad4 NFE exome

AF:

0.0595

Gnomad4 OTH exome

AF:

0.0669

GnomAD4 genome

AF:

0.0774

AC:

11774

AN:

152190

Hom.:

539

Cov.:

AF XY:

0.0797

AC XY:

5928

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0897

Gnomad4 AMR

AF:

0.132

Gnomad4 ASJ

AF:

0.0432

Gnomad4 EAS

AF:

0.123

Gnomad4 SAS

AF:

0.0531

Gnomad4 FIN

AF:

0.0712

Gnomad4 NFE

AF:

0.0596

Gnomad4 OTH

AF:

0.0733

Alfa

AF:

0.0643

Hom.:

416

Bravo

AF:

0.0829

Asia WGS

AF:

0.117

AC:

406

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Benign

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over