rs796052183

Positions:

• chr4-44683304-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP6

The ENST00000281543.6(GUF1):​c.655G>T​(p.Asp219Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000705 in 1,419,278 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: GUF1 ENST00000281543.6 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.77

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 4-44683304-G-T is Benign according to our data. Variant chr4-44683304-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 207915.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GUF1	NM_021927.3	c.655G>T	p.Asp219Tyr	missense_variant	6/17	ENST00000281543.6	NP_068746.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GUF1	ENST00000281543.6	c.655G>T	p.Asp219Tyr	missense_variant	6/17	1	NM_021927.3	ENSP00000281543	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.05e-7 AC: 1 AN: 1419278 Hom.: 0 Cov.: 26 AF XY: 0.00000141 AC XY: 1 AN XY: 707028

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000262

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Long QT syndrome Benign:1

Likely benign, no assertion criteria provided

research

Medical Research Institute, Tokyo Medical and Dental University

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.039	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	T
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-0.50	T
MutationAssessor	Uncertain	2.0	M
MutationTaster	Benign	0.99	N
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.29
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.85	P
Vest4		0.49
MutPred		0.45		Loss of solvent accessibility (P = 0.0807);
MVP		0.80
MPC		0.33
ClinPred		0.97	D
GERP RS		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.23
gMVP		0.52

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: rs796052183; hg19: chr4-44685321;