chr5-74741561-T-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032380.5(GFM2):c.898A>T(p.Ser300Cys) variant causes a missense change. The variant allele was found at a frequency of 0.12 in 1,580,296 control chromosomes in the GnomAD database, including 12,408 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1483 hom., cov: 32)

Exomes 𝑓: 0.12 ( 10925 hom. )

Consequence

GFM2
NM_032380.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.88

Publications

32 publications found

Variant links:

Genes affected

GFM2 (HGNC:29682): (GTP dependent ribosome recycling factor mitochondrial 2) Eukaryotes contain two protein translational systems, one in the cytoplasm and one in the mitochondria. Mitochondrial translation is crucial for maintaining mitochondrial function and mutations in this system lead to a breakdown in the respiratory chain-oxidative phosphorylation system and to impaired maintenance of mitochondrial DNA. This gene encodes one of the mitochondrial translation elongation factors, which is a GTPase that plays a role at the termination of mitochondrial translation by mediating the disassembly of ribosomes from messenger RNA . Its role in the regulation of normal mitochondrial function and in disease states attributed to mitochondrial dysfunction is not known. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2013]

GFM2 Gene-Disease associations (from GenCC):

combined oxidative phosphorylation deficiency 39
Inheritance: AR Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
Leigh syndrome
Inheritance: AR Classification: MODERATE Submitted by: ClinGen

GFM2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016189218).

BP6

Variant 5-74741561-T-A is Benign according to our data. Variant chr5-74741561-T-A is described in ClinVar as Benign. ClinVar VariationId is 137472.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032380.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
GFM2	NM_032380.5	MANE Select	c.898A>T	p.Ser300Cys	missense	Exon 11 of 21	NP_115756.2
GFM2	NM_001281302.2		c.994A>T	p.Ser332Cys	missense	Exon 12 of 22	NP_001268231.1
GFM2	NM_170691.3		c.898A>T	p.Ser300Cys	missense	Exon 11 of 20	NP_733792.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
GFM2	ENST00000296805.8	TSL:1 MANE Select	c.898A>T	p.Ser300Cys	missense	Exon 11 of 21	ENSP00000296805.3
GFM2	ENST00000509430.5	TSL:1	c.898A>T	p.Ser300Cys	missense	Exon 12 of 22	ENSP00000427004.1
GFM2	ENST00000345239.6	TSL:1	c.898A>T	p.Ser300Cys	missense	Exon 11 of 20	ENSP00000296804.3

Frequencies

GnomAD3 genomes

AF:

0.134

AC:

20394

AN:

152014

Hom.:

1483

Cov.:

show subpopulations

Gnomad AFR

AF:

0.182

Gnomad AMI

AF:

0.0943

Gnomad AMR

AF:

0.116

Gnomad ASJ

AF:

0.153

Gnomad EAS

AF:

0.0215

Gnomad SAS

AF:

0.102

Gnomad FIN

AF:

0.106

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.123

Gnomad OTH

AF:

0.151

GnomAD2 exomes

AF:

0.112

AC:

26851

AN:

239636

AF XY:

0.114

show subpopulations

Gnomad AFR exome

AF:

0.178

Gnomad AMR exome

AF:

0.0838

Gnomad ASJ exome

AF:

0.165

Gnomad EAS exome

AF:

0.0228

Gnomad FIN exome

AF:

0.112

Gnomad NFE exome

AF:

0.123

Gnomad OTH exome

AF:

0.131

GnomAD4 exome

AF:

0.119

AC:

169999

AN:

1428164

Hom.:

10925

Cov.:

AF XY:

0.119

AC XY:

84879

AN XY:

711576

show subpopulations

African (AFR)

AF:

0.187

AC:

6059

AN:

32412

American (AMR)

AF:

0.0885

AC:

3815

AN:

43122

Ashkenazi Jewish (ASJ)

AF:

0.162

AC:

4176

AN:

25704

East Asian (EAS)

AF:

0.0154

AC:

605

AN:

39190

South Asian (SAS)

AF:

0.105

AC:

8740

AN:

83076

European-Finnish (FIN)

AF:

0.115

AC:

6122

AN:

53152

Middle Eastern (MID)

AF:

0.207

AC:

1172

AN:

5670

European-Non Finnish (NFE)

AF:

0.121

AC:

131851

AN:

1086612

Other (OTH)

AF:

0.126

AC:

7459

AN:

59226

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

6091

12182

18273

24364

30455

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4732

9464

14196

18928

23660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.134

AC:

20399

AN:

152132

Hom.:

1483

Cov.:

AF XY:

0.133

AC XY:

9914

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.182

AC:

7552

AN:

41500

American (AMR)

AF:

0.116

AC:

1764

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.153

AC:

531

AN:

3468

East Asian (EAS)

AF:

0.0216

AC:

112

AN:

5188

South Asian (SAS)

AF:

0.102

AC:

491

AN:

4828

European-Finnish (FIN)

AF:

0.106

AC:

1124

AN:

10596

Middle Eastern (MID)

AF:

0.197

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.123

AC:

8368

AN:

67964

Other (OTH)

AF:

0.148

AC:

313

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

914

1828

2743

3657

4571

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

218

436

654

872

1090

<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:

0.127

Hom.:

1014

Bravo

AF:

0.139

TwinsUK

AF:

0.133

AC:

492

ALSPAC

AF:

0.124

AC:

477

ESP6500AA

AF:

0.182

AC:

798

ESP6500EA

AF:

0.123

AC:

1051

ExAC

AF:

0.114

AC:

13770

Asia WGS

AF:

0.0720

AC:

248

AN:

3468

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.013

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.92

MetaRNN

Benign

0.0016

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

PhyloP100

3.9

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-2.2

REVEL

Benign

0.17

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.025

Polyphen

0.99

Vest4

0.12

MPC

0.64

ClinPred

0.022

GERP RS

5.9

Varity_R

0.36

gMVP

0.55

Mutation Taster

=90/10

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

2.0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over