rs538769462

Variant names:

• chr4-44678632-C-A
• rs538769462
• NM_021927.3:c.10C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-44678632-C-A
• chr4-44678632-C-G
• chr4-44678632-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021927.3(GUF1):​c.10C>A​(p.Leu4Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000076 in 1,315,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L4V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: GUF1 NM_021927.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.132
• 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]

YIPF7 (HGNC:26825): (Yip1 domain family member 7) Predicted to be involved in endoplasmic reticulum to Golgi vesicle-mediated transport and vesicle fusion with Golgi apparatus. Predicted to be located in endoplasmic reticulum membrane. Predicted to be integral component of membrane. Predicted to be active in trans-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.068973124).

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.10C>A	p.Leu4Ile	missense	Exon 1 of 17	NP_068746.2	Q8N442
	GUF1	NM_001345868.2		c.10C>A	p.Leu4Ile	missense	Exon 1 of 16	NP_001332797.1
	GUF1	NM_001345867.2		c.-959C>A		5_prime_UTR	Exon 1 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.10C>A	p.Leu4Ile	missense	Exon 1 of 17	ENSP00000281543.5	Q8N442
	GUF1	ENST00000513775.1	TSL:1	n.10C>A		non_coding_transcript_exon	Exon 1 of 9	ENSP00000422681.1	D6RBJ0
	YIPF7	ENST00000953307.1		c.-856G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	ENSP00000623366.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.60e-7 AC: 1 AN: 1315594 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 646630

African (AFR) AF: 0.00 AC: 0 AN: 25744

American (AMR) AF: 0.00 AC: 0 AN: 17960

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19368

East Asian (EAS) AF: 0.00 AC: 0 AN: 31286

South Asian (SAS) AF: 0.00 AC: 0 AN: 60144

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48292

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4146

European-Non Finnish (NFE) AF: 9.48e-7 AC: 1 AN: 1054728

Other (OTH) AF: 0.00 AC: 0 AN: 53926

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	6.6
DANN	Uncertain	0.98
DEOGEN2	Benign	0.050	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.13
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.041
Sift	Benign	0.058	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.043	B
Vest4		0.18
MutPred		0.28		Gain of sheet (P = 0.0266)
MVP		0.19
MPC		0.066
ClinPred		0.066	T
GERP RS		0.23
PromoterAI		0.17	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.063
gMVP		0.49
Mutation Taster		=97/3	polymorphism

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: rs538769462; hg19: chr4-44680649;