3-122363019-C-G

Position:

• chr3-122363019-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000291458.9(MIX23):​c.333G>C​(p.Trp111Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: MIX23 ENST00000291458.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.21

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 (HGNC:):

ACMG classification

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=0.25115004).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIX23	NM_001017928.4	c.333G>C	p.Trp111Cys	missense_variant	4/5	ENST00000291458.9	NP_001017928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIX23	ENST00000291458.9	c.333G>C	p.Trp111Cys	missense_variant	4/5	1	NM_001017928.4	ENSP00000291458.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 12, 2024

The c.333G>C (p.W111C) alteration is located in exon 4 (coding exon 4) of the CCDC58 gene. This alteration results from a G to C substitution at nucleotide position 333, causing the tryptophan (W) at amino acid position 111 to be replaced by a cysteine (C). 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	0.93
BayesDel_addAF	Uncertain	0.094	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T;.;T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Pathogenic	0.98	D;D;D
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.69	N;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.050	N;N;N
REVEL	Benign	0.15
Sift	Uncertain	0.0050	D;D;D
Sift4G	Benign	0.079	T;D;T
Polyphen		0.73	P;.;.
Vest4		0.49
MutPred		0.56		Loss of catalytic residue at L109 (P = 0.0036);.;.;
MVP		0.47
MPC		1.1
ClinPred		0.75	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.30
gMVP		0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-122081866;