19-19096189-C-G

Variant names:

• chr19-19096189-C-G
• NM_178526.5:c.65C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC25A42 NM_178526.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.926

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]

ACMG classification

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=0.35599452).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A42	NM_178526.5	c.65C>G	p.Ser22Trp	missense_variant	Exon 2 of 8	ENST00000318596.8	NP_848621.2
SLC25A42	NM_001321544.2	c.65C>G	p.Ser22Trp	missense_variant	Exon 2 of 8		NP_001308473.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A42	ENST00000318596.8	c.65C>G	p.Ser22Trp	missense_variant	Exon 2 of 8	1	NM_178526.5	ENSP00000326693.6
SLC25A42	ENST00000594070.5	n.247C>G		non_coding_transcript_exon_variant	Exon 1 of 5	2
SLC25A42	ENST00000597661.5	n.128C>G		non_coding_transcript_exon_variant	Exon 2 of 5	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461518 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727012

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.074	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.79	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	1.6	L
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.23
Sift	Benign	0.14	T
Sift4G	Benign	0.18	T
Polyphen		0.85	P
Vest4		0.44
MutPred		0.43		Loss of disorder (P = 8e-04);
MVP		0.55
MPC		1.5
ClinPred		0.46	T
GERP RS		1.9
Varity_R		0.052
gMVP		0.63

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-19206998;