4-44686523-CGC-TGT

Variant names:

• chr4-44686523-CGC-TGT
• NM_021927.3:c.748_750delCGCinsTGT
• GUF1 p.Arg250Cys

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_021927.3(GUF1):​c.748_750delCGCinsTGT​(p.Arg250Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R250L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GUF1 NM_021927.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021927.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GUF1	NM_021927.3	MANE Select	c.748_750delCGCinsTGT	p.Arg250Cys	missense	N/A	NP_068746.2	Q8N442
	GUF1	NM_001345868.2		c.748_750delCGCinsTGT	p.Arg250Cys	missense	N/A	NP_001332797.1
	GUF1	NM_001345867.2		c.-225_-223delCGCinsTGT		5_prime_UTR	Exon 8 of 17	NP_001332796.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GUF1	ENST00000281543.6	TSL:1 MANE Select	c.748_750delCGCinsTGT	p.Arg250Cys	missense	N/A	ENSP00000281543.5	Q8N442
	GUF1	ENST00000513775.1	TSL:1	n.*339_*341delCGCinsTGT		non_coding_transcript_exon	Exon 7 of 9	ENSP00000422681.1	D6RBJ0
	GUF1	ENST00000513775.1	TSL:1	n.*339_*341delCGCinsTGT		3_prime_UTR	Exon 7 of 9	ENSP00000422681.1	D6RBJ0

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr4-44688540;