19-19096128-G-T

Variant summary

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

The NM_178526.5(SLC25A42):​c.4G>T​(p.Gly2Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SLC25A42
NM_178526.5 missense

Scores

1
11
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.50
Variant links:
Genes affected
SLC25A42 (HGNC:28380): (solute carrier family 25 member 42) This gene encodes a solute carrier family 25 protein. Solute carrier family 25 proteins are localized to mitochondria and play critical roles in the transport of molecules across the inner mitochondrial membrane. The encoded protein is a mitochondrial transporter for coenzyme A (CoA) and adenosine 3',5'-diphosphate. [provided by RefSeq, Feb 2012]

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
SLC25A42NM_178526.5 linkc.4G>T p.Gly2Cys missense_variant Exon 2 of 8 ENST00000318596.8 NP_848621.2 Q86VD7A0A024R7K2Q8NHH2
SLC25A42NM_001321544.2 linkc.4G>T p.Gly2Cys missense_variant Exon 2 of 8 NP_001308473.1 Q86VD7A0A024R7K2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC25A42ENST00000318596.8 linkc.4G>T p.Gly2Cys missense_variant Exon 2 of 8 1 NM_178526.5 ENSP00000326693.6 Q86VD7
SLC25A42ENST00000594070.5 linkn.186G>T non_coding_transcript_exon_variant Exon 1 of 5 2
SLC25A42ENST00000597661.5 linkn.67G>T non_coding_transcript_exon_variant Exon 2 of 5 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
Jul 03, 2022
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This sequence change replaces glycine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 2 of the SLC25A42 protein (p.Gly2Cys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SLC25A42-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.23
BayesDel_addAF
Uncertain
0.065
T
BayesDel_noAF
Benign
-0.14
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.020
T
Eigen
Uncertain
0.31
Eigen_PC
Uncertain
0.32
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.55
T
M_CAP
Uncertain
0.093
D
MetaRNN
Uncertain
0.60
D
MetaSVM
Uncertain
0.12
D
MutationAssessor
Benign
1.9
L
PrimateAI
Uncertain
0.69
T
PROVEAN
Benign
-1.1
N
REVEL
Uncertain
0.41
Sift
Uncertain
0.010
D
Sift4G
Uncertain
0.056
T
Polyphen
0.88
P
Vest4
0.58
MutPred
0.35
Loss of ubiquitination at K6 (P = 0.0356);
MVP
0.60
MPC
1.4
ClinPred
0.92
D
GERP RS
3.7
Varity_R
0.20
gMVP
0.64

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-19206937; API