Genetic Variant GUF1:p.Ala19Ala (chr4-44678679-C-T) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_021927.3(GUF1):c.57C>T(p.Ala19Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000004 in 1,500,688 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: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

GUF1
NM_021927.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0900

Publications

0 publications found

Variant links:

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]

GUF1 links:

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]

YIPF7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 4-44678679-C-T is Benign according to our data. Variant chr4-44678679-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 744814.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.09 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GUF1	NM_021927.3	MANE Select	c.57C>T	p.Ala19Ala	synonymous	Exon 1 of 17	NP_068746.2	Q8N442
GUF1	NM_001345868.2		c.57C>T	p.Ala19Ala	synonymous	Exon 1 of 16	NP_001332797.1
GUF1	NM_001345867.2		c.-912C>T		5_prime_UTR	Exon 1 of 17	NP_001332796.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GUF1	ENST00000281543.6	TSL:1 MANE Select	c.57C>T	p.Ala19Ala	synonymous	Exon 1 of 17	ENSP00000281543.5	Q8N442
GUF1	ENST00000513775.1	TSL:1	n.57C>T		non_coding_transcript_exon	Exon 1 of 9	ENSP00000422681.1	D6RBJ0
GUF1	ENST00000953400.1		c.57C>T	p.Ala19Ala	synonymous	Exon 1 of 17	ENSP00000623459.1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000964

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

131064

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000148

AC:

AN:

1348446

Hom.:

Cov.:

AF XY:

0.00000150

AC XY:

AN XY:

666878

show subpopulations

African (AFR)

AF:

0.0000382

AC:

AN:

26162

American (AMR)

AF:

0.00

AC:

AN:

19372

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22248

East Asian (EAS)

AF:

0.00

AC:

AN:

31716

South Asian (SAS)

AF:

0.00

AC:

AN:

67100

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50302

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5124

European-Non Finnish (NFE)

AF:

9.34e-7

AC:

AN:

1070936

Other (OTH)

AF:

0.00

AC:

AN:

55486

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.0000964

AC:

AN:

41478

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000302

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

7.4

(source)

DANN

Benign

0.83

PhyloP100

0.090

PromoterAI

0.016

Neutral

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over