chr19-19076766-C-T

Variant names:

• chr19-19076766-C-T
• rs12985799
• NM_178526.5:c.-35+12651C>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.-35+12651C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 152,130 control chromosomes in the GnomAD database, including 46,781 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 0.78 (46781 hom., cov: 33)
• Consequence: SLC25A42 NM_178526.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.967
• Publications: 8 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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

ENSG00000296554 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A42	NM_178526.5	MANE Select	c.-35+12651C>T		intron	N/A	NP_848621.2
	SLC25A42	NM_001321544.2		c.-35+12720C>T		intron	N/A	NP_001308473.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A42	ENST00000318596.8	TSL:1 MANE Select	c.-35+12651C>T		intron	N/A	ENSP00000326693.6
	SLC25A42	ENST00000857041.1		c.-35+12720C>T		intron	N/A	ENSP00000527100.1
	SLC25A42	ENST00000857042.1		c.-132-9920C>T		intron	N/A	ENSP00000527101.1

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118605 AN: 152010 Hom.: 46756 Cov.: 33

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.936

Gnomad AMR AF: 0.830

Gnomad ASJ AF: 0.847

Gnomad EAS AF: 0.890

Gnomad SAS AF: 0.813

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.824

Gnomad OTH AF: 0.812

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

GnomAD4 genome AF: 0.780 AC: 118685 AN: 152130 Hom.: 46781 Cov.: 33 AF XY: 0.780 AC XY: 58014 AN XY: 74372

African (AFR) AF: 0.665 AC: 27588 AN: 41470

American (AMR) AF: 0.830 AC: 12674 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.847 AC: 2942 AN: 3472

East Asian (EAS) AF: 0.890 AC: 4608 AN: 5176

South Asian (SAS) AF: 0.814 AC: 3931 AN: 4828

European-Finnish (FIN) AF: 0.765 AC: 8093 AN: 10576

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.824 AC: 56052 AN: 68014

Other (OTH) AF: 0.809 AC: 1711 AN: 2114

Alfa AF: 0.741 Hom.: 4057

Bravo AF: 0.783

Asia WGS AF: 0.830 AC: 2888 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.4
DANN	Benign	0.41
PhyloP100		0.97
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: rs12985799; hg19: chr19-19187575;