4-44685384-A-G

Variant names:

• chr4-44685384-A-G
• rs12499960
• NM_021927.3:c.670-575A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.752
• Publications: 18 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
GUF1	NM_021927.3	c.670-575A>G		intron_variant	Intron 6 of 16	ENST00000281543.6	NP_068746.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GUF1	ENST00000281543.6	c.670-575A>G		intron_variant	Intron 6 of 16	1	NM_021927.3	ENSP00000281543.5

Frequencies

GnomAD3 genomes AF: 0.746 AC: 113269 AN: 151854 Hom.: 42641 Cov.: 32

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

African (AFR) AF: 0.662 AC: 27445 AN: 41456

American (AMR) AF: 0.814 AC: 12410 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.737 AC: 2556 AN: 3468

East Asian (EAS) AF: 0.775 AC: 4005 AN: 5168

South Asian (SAS) AF: 0.661 AC: 3189 AN: 4822

European-Finnish (FIN) AF: 0.845 AC: 8953 AN: 10596

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.770 AC: 52306 AN: 67906

Other (OTH) AF: 0.744 AC: 1570 AN: 2110

Alfa AF: 0.760 Hom.: 92067

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
PhyloP100		-0.75
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12499960; hg19: chr4-44687401;