4-44683219-AT-A

Position:

• chr4-44683219-AT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_021927.3(GUF1):​c.586-5delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 1,077,236 control chromosomes in the GnomAD database, including 3,191 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.070 (396 hom., cov: 30)
  • Exomes 𝑓: 0.11 (2795 hom.)
• Consequence: GUF1 NM_021927.3 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0310

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]

GUF1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 4-44683219-AT-A is Benign according to our data. Variant chr4-44683219-AT-A is described in ClinVar as [Benign]. Clinvar id is 1601230.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GUF1	NM_021927.3	c.586-5delT		splice_region_variant, intron_variant		ENST00000281543.6	NP_068746.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GUF1	ENST00000281543.6	c.586-5delT		splice_region_variant, intron_variant		1	NM_021927.3	ENSP00000281543.5

Frequencies

GnomAD3 genomes AF: 0.0700 AC: 10391 AN: 148468 Hom.: 398 Cov.: 30

Gnomad AFR AF: 0.0721

Gnomad AMI AF: 0.0311

Gnomad AMR AF: 0.0837

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.0403

Gnomad FIN AF: 0.0704

Gnomad MID AF: 0.0548

Gnomad NFE AF: 0.0581

Gnomad OTH AF: 0.0742

GnomAD4 exome AF: 0.107 AC: 99383 AN: 928682 Hom.: 2795 Cov.: 15 AF XY: 0.106 AC XY: 49252 AN XY: 463128

Gnomad4 AFR exome AF: 0.115

Gnomad4 AMR exome AF: 0.144

Gnomad4 ASJ exome AF: 0.214

Gnomad4 EAS exome AF: 0.194

Gnomad4 SAS exome AF: 0.0842

Gnomad4 FIN exome AF: 0.106

Gnomad4 NFE exome AF: 0.101

Gnomad4 OTH exome AF: 0.117

GnomAD4 genome AF: 0.0700 AC: 10393 AN: 148554 Hom.: 396 Cov.: 30 AF XY: 0.0712 AC XY: 5159 AN XY: 72434

Gnomad4 AFR AF: 0.0723

Gnomad4 AMR AF: 0.0834

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.0393

Gnomad4 FIN AF: 0.0704

Gnomad4 NFE AF: 0.0581

Gnomad4 OTH AF: 0.0735

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs371225473; hg19: chr4-44685236;