19-19097431-C-T

Variant names:

• chr19-19097431-C-T
• rs2012318
• NM_178526.5:c.81+1226C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178526.5(SLC25A42):​c.81+1226C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.77 in 152,176 control chromosomes in the GnomAD database, including 45,677 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.77 (45677 hom., cov: 33)
• Consequence: SLC25A42 NM_178526.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.305
• Publications: 6 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

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.81+1226C>T		intron	N/A	NP_848621.2	Q86VD7
	SLC25A42	NM_001321544.2		c.81+1226C>T		intron	N/A	NP_001308473.1	Q86VD7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A42	ENST00000318596.8	TSL:1 MANE Select	c.81+1226C>T		intron	N/A	ENSP00000326693.6	Q86VD7
	SLC25A42	ENST00000857041.1		c.81+1226C>T		intron	N/A	ENSP00000527100.1
	SLC25A42	ENST00000857042.1		c.81+1226C>T		intron	N/A	ENSP00000527101.1

Frequencies

GnomAD3 genomes AF: 0.770 AC: 117100 AN: 152058 Hom.: 45658 Cov.: 33

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.935

Gnomad AMR AF: 0.818

Gnomad ASJ AF: 0.830

Gnomad EAS AF: 0.890

Gnomad SAS AF: 0.811

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.819

Gnomad OTH AF: 0.801

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.770 AC: 117163 AN: 152176 Hom.: 45677 Cov.: 33 AF XY: 0.770 AC XY: 57284 AN XY: 74386

African (AFR) AF: 0.643 AC: 26673 AN: 41498

American (AMR) AF: 0.819 AC: 12519 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.830 AC: 2879 AN: 3470

East Asian (EAS) AF: 0.890 AC: 4606 AN: 5174

South Asian (SAS) AF: 0.812 AC: 3921 AN: 4826

European-Finnish (FIN) AF: 0.765 AC: 8097 AN: 10588

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.819 AC: 55700 AN: 68008

Other (OTH) AF: 0.799 AC: 1689 AN: 2114

Alfa AF: 0.784 Hom.: 7082

Bravo AF: 0.772

Asia WGS AF: 0.826 AC: 2876 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.0
DANN	Benign	0.63
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2012318; hg19: chr19-19208240;