4-44678682-T-C

Variant names:

• chr4-44678682-T-C
• rs2109624059
• NM_021927.3:c.60T>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_021927.3(GUF1):​c.60T>C​(p.Thr20Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000741 in 1,349,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: GUF1 NM_021927.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.03
• 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 4-44678682-T-C is Benign according to our data. Variant chr4-44678682-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1652988.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.03 with no splicing effect.

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.60T>C	p.Thr20Thr	synonymous	Exon 1 of 17	NP_068746.2	Q8N442
	GUF1	NM_001345868.2		c.60T>C	p.Thr20Thr	synonymous	Exon 1 of 16	NP_001332797.1
	GUF1	NM_001345867.2		c.-909T>C		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.60T>C	p.Thr20Thr	synonymous	Exon 1 of 17	ENSP00000281543.5	Q8N442
	GUF1	ENST00000513775.1	TSL:1	n.60T>C		non_coding_transcript_exon	Exon 1 of 9	ENSP00000422681.1	D6RBJ0
	GUF1	ENST00000953400.1		c.60T>C	p.Thr20Thr	synonymous	Exon 1 of 17	ENSP00000623459.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.41e-7 AC: 1 AN: 1349200 Hom.: 0 Cov.: 31 AF XY: 0.00000150 AC XY: 1 AN XY: 667332

African (AFR) AF: 0.00 AC: 0 AN: 26180

American (AMR) AF: 0.0000513 AC: 1 AN: 19488

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22330

East Asian (EAS) AF: 0.00 AC: 0 AN: 31730

South Asian (SAS) AF: 0.00 AC: 0 AN: 67158

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5162

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1071248

Other (OTH) AF: 0.00 AC: 0 AN: 55544

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.33
DANN	Benign	0.34
PhyloP100		-3.0
PromoterAI		-0.064	Neutral

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: rs2109624059; hg19: chr4-44680699;