4-44683219-A-AT

Position:

• chr4-44683219-A-AT

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_021927.3(GUF1):​c.586-5dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 1,133,382 control chromosomes in the GnomAD database, including 2 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00051 (0 hom., cov: 30)
  • Exomes 𝑓: 0.012 (2 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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 4-44683219-A-AT is Benign according to our data. Variant chr4-44683219-A-AT is described in ClinVar as [Benign]. Clinvar id is 1644706.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.000505 AC: 75 AN: 148630 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000370

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00121

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000391

Gnomad SAS AF: 0.000424

Gnomad FIN AF: 0.000203

Gnomad MID AF: 0.00968

Gnomad NFE AF: 0.000463

Gnomad OTH AF: 0.000987

GnomAD4 exome AF: 0.0119 AC: 11738 AN: 984668 Hom.: 2 Cov.: 15 AF XY: 0.0115 AC XY: 5686 AN XY: 492856

Gnomad4 AFR exome AF: 0.00990

Gnomad4 AMR exome AF: 0.0109

Gnomad4 ASJ exome AF: 0.00750

Gnomad4 EAS exome AF: 0.00621

Gnomad4 SAS exome AF: 0.0124

Gnomad4 FIN exome AF: 0.00269

Gnomad4 NFE exome AF: 0.0129

Gnomad4 OTH exome AF: 0.0113

GnomAD4 genome AF: 0.000511 AC: 76 AN: 148714 Hom.: 0 Cov.: 30 AF XY: 0.000565 AC XY: 41 AN XY: 72510

Gnomad4 AFR AF: 0.000394

Gnomad4 AMR AF: 0.00121

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000392

Gnomad4 SAS AF: 0.000426

Gnomad4 FIN AF: 0.000203

Gnomad4 NFE AF: 0.000463

Gnomad4 OTH AF: 0.000978

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

Jan 20, 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;