Variant 3-122359879-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001017928.4(MIX23):c.425A>C(p.Lys142Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000713 in 1,402,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

MIX23
NM_001017928.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.72

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]

MIX23 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3807374).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MIX23	NM_001017928.4 linkuse as main transcript	c.425A>C	p.Lys142Thr	missense_variant	5/5	ENST00000291458.9	NP_001017928.1
MIX23	NM_001308326.2 linkuse as main transcript	c.383A>C	p.Lys128Thr	missense_variant	5/5		NP_001295255.1
MIX23	XM_047447427.1 linkuse as main transcript	c.395A>C	p.Lys132Thr	missense_variant	6/6		XP_047303383.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIX23	ENST00000291458.9 linkuse as main transcript	c.425A>C	p.Lys142Thr	missense_variant	5/5	1	NM_001017928.4	ENSP00000291458	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000472

AC:

AN:

211750

Hom.:

AF XY:

0.00000861

AC XY:

AN XY:

116102

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000975

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.13e-7

AC:

AN:

1402210

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

698162

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.000111

Hom.:

ExAC

AF:

0.00000824

AC:

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 submitter

clinical testing

Ambry Genetics

Nov 07, 2022

The c.425A>C (p.K142T) alteration is located in exon 5 (coding exon 5) of the CCDC58 gene. This alteration results from a A to C substitution at nucleotide position 425, causing the lysine (K) at amino acid position 142 to be replaced by a threonine (T). 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

0.20

BayesDel_addAF

Uncertain

0.094

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.045

T;.;T

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.88

D;D;D

M_CAP

Benign

0.0091

MetaRNN

Benign

0.38

T;T;T

MetaSVM

Benign

-0.63

MutationAssessor

Benign

1.7

L;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.2

N;D;N

REVEL

Benign

0.25

Sift

Benign

0.050

D;D;T

Sift4G

Uncertain

0.010

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.54

MutPred

0.47

Loss of glycosylation at P141 (P = 0.0053);.;.;

MVP

0.50

MPC

1.5

ClinPred

0.83

GERP RS

4.8

Varity_R

0.20

gMVP

0.70

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over