chr4-139266793-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_032623.4(MGARP):​c.529C>T​(p.Pro177Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000146 in 1,614,130 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00015 ( 1 hom. )

Consequence

MGARP
NM_032623.4 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0370
Variant links:
Genes affected
MGARP (HGNC:29969): (mitochondria localized glutamic acid rich protein) Predicted to be involved in several processes, including axonal transport; cellular response to hormone stimulus; and protein targeting to mitochondrion. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.008718342).
BP6
Variant 4-139266793-G-A is Benign according to our data. Variant chr4-139266793-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2392222.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MGARPNM_032623.4 linkuse as main transcriptc.529C>T p.Pro177Ser missense_variant 4/4 ENST00000398955.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MGARPENST00000398955.2 linkuse as main transcriptc.529C>T p.Pro177Ser missense_variant 4/41 NM_032623.4 P1

Frequencies

GnomAD3 genomes
AF:
0.000131
AC:
20
AN:
152118
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000118
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000208
AC:
52
AN:
249582
Hom.:
0
AF XY:
0.000236
AC XY:
32
AN XY:
135406
show subpopulations
Gnomad AFR exome
AF:
0.0000646
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000915
Gnomad FIN exome
AF:
0.0000464
Gnomad NFE exome
AF:
0.000185
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.000147
AC:
215
AN:
1461894
Hom.:
1
Cov.:
31
AF XY:
0.000198
AC XY:
144
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000881
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000111
Gnomad4 OTH exome
AF:
0.000215
GnomAD4 genome
AF:
0.000131
AC:
20
AN:
152236
Hom.:
0
Cov.:
32
AF XY:
0.000161
AC XY:
12
AN XY:
74428
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000155
Hom.:
0
Bravo
AF:
0.0000869
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000241
AC:
2
ExAC
AF:
0.000190
AC:
23
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.000178

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsJul 13, 2022This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.080
BayesDel_addAF
Benign
-0.62
T
BayesDel_noAF
Benign
-0.73
CADD
Benign
0.94
DANN
Benign
0.79
DEOGEN2
Benign
0.0029
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.044
N
LIST_S2
Benign
0.37
T
M_CAP
Benign
0.0042
T
MetaRNN
Benign
0.0087
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.35
N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.21
T
PROVEAN
Benign
-0.95
N
REVEL
Benign
0.034
Sift
Benign
0.98
T
Sift4G
Benign
0.78
T
Polyphen
0.0040
B
Vest4
0.021
MVP
0.048
MPC
0.17
ClinPred
0.017
T
GERP RS
3.5
Varity_R
0.025
gMVP
0.066

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs148366930; hg19: chr4-140187947; API