Genetic Variant NM_152407.4:c.67T>C (chr5-149345606-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_152407.4(GRPEL2):c.67T>C(p.Trp23Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000161 in 1,610,136 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00015 ( 1 hom. )

Consequence

GRPEL2
NM_152407.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.189

Publications

1 publications found

Variant links:

Genes affected

GRPEL2 (HGNC:21060): (GrpE like 2, mitochondrial) Predicted to enable adenyl-nucleotide exchange factor activity and unfolded protein binding activity. Predicted to be involved in protein import into mitochondrial matrix. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

GRPEL2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0048662424).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152407.4. 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
	GRPEL2	NM_152407.4	MANE Select	c.67T>C	p.Trp23Arg	missense	Exon 1 of 4	NP_689620.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GRPEL2	ENST00000329271.8	TSL:1 MANE Select	c.67T>C	p.Trp23Arg	missense	Exon 1 of 4	ENSP00000329558.3	Q8TAA5-1
GRPEL2	ENST00000913747.1		c.67T>C	p.Trp23Arg	missense	Exon 1 of 4	ENSP00000583806.1
GRPEL2	ENST00000513661.5	TSL:2	c.67T>C	p.Trp23Arg	missense	Exon 1 of 3	ENSP00000426331.1	D6RGI6

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

152058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000276

AC:

AN:

239178

AF XY:

0.000246

show subpopulations

Gnomad AFR exome

AF:

0.000203

Gnomad AMR exome

AF:

0.000177

Gnomad ASJ exome

AF:

0.00531

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000465

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000150

AC:

219

AN:

1457960

Hom.:

Cov.:

AF XY:

0.000142

AC XY:

103

AN XY:

724884

show subpopulations

African (AFR)

AF:

0.0000598

AC:

AN:

33424

American (AMR)

AF:

0.000248

AC:

AN:

44400

Ashkenazi Jewish (ASJ)

AF:

0.00576

AC:

150

AN:

26032

East Asian (EAS)

AF:

0.00

AC:

AN:

39592

South Asian (SAS)

AF:

0.00

AC:

AN:

85482

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52882

Middle Eastern (MID)

AF:

0.000186

AC:

AN:

5370

European-Non Finnish (NFE)

AF:

0.0000234

AC:

AN:

1110676

Other (OTH)

AF:

0.000483

AC:

AN:

60102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

GnomAD4 genome

AF:

0.000263

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.000193

AC:

AN:

41524

American (AMR)

AF:

0.000261

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00720

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

67988

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

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:

0.000277

Hom.:

Bravo

AF:

0.000302

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000582

AC:

ExAC

AF:

0.000198

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.66

CADD

Benign

6.5

(source)

DANN

Benign

0.56

DEOGEN2

Benign

0.020

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.37

M_CAP

Benign

0.0020

MetaRNN

Benign

0.0049

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

PhyloP100

-0.19

PrimateAI

Benign

0.36

PROVEAN

Benign

0.080

REVEL

Benign

0.0070

Sift

Benign

0.40

Sift4G

Benign

0.37

Polyphen

0.0

Vest4

0.13

MutPred

0.41

Gain of disorder (P = 0.0064)

MVP

0.31

MPC

0.39

ClinPred

0.0045

GERP RS

-0.61

PromoterAI

0.10

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.081

gMVP

0.23

Mutation Taster

=93/7

polymorphism

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over