chr4-139266790-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032623.4(MGARP):​c.532G>A​(p.Glu178Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

MGARP
NM_032623.4 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.38
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2079454).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MGARPNM_032623.4 linkuse as main transcriptc.532G>A p.Glu178Lys missense_variant 4/4 ENST00000398955.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MGARPENST00000398955.2 linkuse as main transcriptc.532G>A p.Glu178Lys missense_variant 4/41 NM_032623.4 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000958
AC:
14
AN:
1461894
Hom.:
0
Cov.:
31
AF XY:
0.00000688
AC XY:
5
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000126
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsNov 16, 2021The c.532G>A (p.E178K) alteration is located in exon 4 (coding exon 4) of the MGARP gene. This alteration results from a G to A substitution at nucleotide position 532, causing the glutamic acid (E) at amino acid position 178 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.099
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.060
T
Eigen
Benign
-0.34
Eigen_PC
Benign
-0.43
FATHMM_MKL
Benign
0.18
N
LIST_S2
Benign
0.66
T
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.21
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.2
M
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.33
T
PROVEAN
Uncertain
-2.7
D
REVEL
Benign
0.066
Sift
Uncertain
0.017
D
Sift4G
Uncertain
0.011
D
Polyphen
0.87
P
Vest4
0.12
MutPred
0.44
Gain of loop (P = 0.0013);
MVP
0.31
MPC
0.38
ClinPred
0.94
D
GERP RS
3.6
Varity_R
0.20
gMVP
0.20

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs754607391; hg19: chr4-140187944; API