Genetic Variant SLC25A42:p.Ser22Trp (chr19-19096189-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_178526.5(SLC25A42):c.65C>G(p.Ser22Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,518 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S22L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLC25A42
NM_178526.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.926

Publications

0 publications found

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]

SLC25A42 Gene-Disease associations (from GenCC):

metabolic crises, recurrent, with variable encephalomyopathic features and neurologic regression
Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia

SLC25A42 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35599452).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178526.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A42	NM_178526.5	MANE Select	c.65C>G	p.Ser22Trp	missense	Exon 2 of 8	NP_848621.2	Q86VD7
	SLC25A42	NM_001321544.2		c.65C>G	p.Ser22Trp	missense	Exon 2 of 8	NP_001308473.1	Q86VD7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC25A42	ENST00000318596.8	TSL:1 MANE Select	c.65C>G	p.Ser22Trp	missense	Exon 2 of 8	ENSP00000326693.6	Q86VD7
SLC25A42	ENST00000857041.1		c.65C>G	p.Ser22Trp	missense	Exon 2 of 8	ENSP00000527100.1
SLC25A42	ENST00000857042.1		c.65C>G	p.Ser22Trp	missense	Exon 3 of 9	ENSP00000527101.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461518

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727012

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111748

Other (OTH)

AF:

0.00

AC:

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.062

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.074

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.79

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.36

MetaSVM

Benign

-0.62

MutationAssessor

Benign

1.6

PhyloP100

0.93

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.8

REVEL

Benign

0.23

Sift

Benign

0.14

Sift4G

Benign

0.18

Polyphen

0.85

Vest4

0.44

MutPred

0.43

Loss of disorder (P = 8e-04)

MVP

0.55

MPC

1.5

ClinPred

0.46

GERP RS

1.9

Varity_R

0.052

gMVP

0.63

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over