3-122359906-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001017928.4(MIX23):​c.398G>A​(p.Arg133His) variant causes a missense change. The variant allele was found at a frequency of 0.0000401 in 1,569,856 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000068 ( 1 hom., cov: 31)
Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

MIX23
NM_001017928.4 missense

Scores

4
11
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.06
Variant links:
Genes affected
MIX23 (HGNC:31136): (mitochondrial matrix import factor 23) Predicted to be located in mitochondrial intermembrane space. Predicted to be active in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MIX23NM_001017928.4 linkc.398G>A p.Arg133His missense_variant Exon 5 of 5 ENST00000291458.9 NP_001017928.1 Q4VC31
MIX23NM_001308326.2 linkc.356G>A p.Arg119His missense_variant Exon 5 of 5 NP_001295255.1 Q4VC31C9JQ41
MIX23XM_047447427.1 linkc.368G>A p.Arg123His missense_variant Exon 6 of 6 XP_047303383.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MIX23ENST00000291458.9 linkc.398G>A p.Arg133His missense_variant Exon 5 of 5 1 NM_001017928.4 ENSP00000291458.5 Q4VC31

Frequencies

GnomAD3 genomes
AF:
0.0000677
AC:
10
AN:
147736
Hom.:
1
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000251
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000642
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000892
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000361
AC:
8
AN:
221646
Hom.:
0
AF XY:
0.0000495
AC XY:
6
AN XY:
121200
show subpopulations
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 SAS exome
AF:
0.000316
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000373
AC:
53
AN:
1422120
Hom.:
0
Cov.:
34
AF XY:
0.0000467
AC XY:
33
AN XY:
707366
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:
0.000377
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000201
Gnomad4 OTH exome
AF:
0.0000171
GnomAD4 genome
AF:
0.0000677
AC:
10
AN:
147736
Hom.:
1
Cov.:
31
AF XY:
0.0000697
AC XY:
5
AN XY:
71742
show subpopulations
Gnomad4 AFR
AF:
0.0000251
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000642
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000892
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000658
Hom.:
0
Bravo
AF:
0.0000302
ExAC
AF:
0.0000659
AC:
8

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 21, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.398G>A (p.R133H) alteration is located in exon 5 (coding exon 5) of the CCDC58 gene. This alteration results from a G to A substitution at nucleotide position 398, causing the arginine (R) at amino acid position 133 to be replaced by a histidine (H). 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
Pathogenic
0.96
BayesDel_addAF
Uncertain
0.038
T
BayesDel_noAF
Uncertain
0.12
CADD
Pathogenic
29
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.32
T;.;T
Eigen
Pathogenic
0.76
Eigen_PC
Pathogenic
0.71
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.96
D;D;D
M_CAP
Benign
0.018
T
MetaRNN
Uncertain
0.43
T;T;T
MetaSVM
Uncertain
-0.11
T
MutationAssessor
Uncertain
2.5
M;.;.
PrimateAI
Uncertain
0.75
T
PROVEAN
Uncertain
-3.4
D;D;D
REVEL
Uncertain
0.42
Sift
Benign
0.054
T;D;D
Sift4G
Uncertain
0.0090
D;D;D
Polyphen
1.0
D;.;.
Vest4
0.51
MVP
0.59
MPC
1.6
ClinPred
0.86
D
GERP RS
4.7
Varity_R
0.33
gMVP
0.95

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs748569885; hg19: chr3-122078753; API