19-19100429-C-T

Variant names:

• chr19-19100429-C-T
• rs11666627
• NM_178526.5:c.82-1352C>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.82-1352C>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 151,920 control chromosomes in the GnomAD database, including 45,624 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 (45624 hom., cov: 30)
• Consequence: SLC25A42 NM_178526.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.642
• Publications: 4 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

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 = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A42	NM_178526.5	c.82-1352C>T		intron_variant	Intron 2 of 7	ENST00000318596.8	NP_848621.2
SLC25A42	NM_001321544.2	c.82-1352C>T		intron_variant	Intron 2 of 7		NP_001308473.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A42	ENST00000318596.8	c.82-1352C>T		intron_variant	Intron 2 of 7	1	NM_178526.5	ENSP00000326693.6
SLC25A42	ENST00000594070.5	n.264-1352C>T		intron_variant	Intron 1 of 4	2
SLC25A42	ENST00000597661.5	n.144+4224C>T		intron_variant	Intron 2 of 4	3

Frequencies

GnomAD3 genomes AF: 0.770 AC: 116930 AN: 151802 Hom.: 45605 Cov.: 30

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.935

Gnomad AMR AF: 0.818

Gnomad ASJ AF: 0.830

Gnomad EAS AF: 0.889

Gnomad SAS AF: 0.812

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: 116993 AN: 151920 Hom.: 45624 Cov.: 30 AF XY: 0.770 AC XY: 57182 AN XY: 74248

African (AFR) AF: 0.643 AC: 26621 AN: 41392

American (AMR) AF: 0.819 AC: 12494 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.830 AC: 2880 AN: 3470

East Asian (EAS) AF: 0.890 AC: 4578 AN: 5144

South Asian (SAS) AF: 0.813 AC: 3912 AN: 4814

European-Finnish (FIN) AF: 0.765 AC: 8091 AN: 10576

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

European-Non Finnish (NFE) AF: 0.819 AC: 55650 AN: 67944

Other (OTH) AF: 0.799 AC: 1688 AN: 2112

Alfa AF: 0.786 Hom.: 6113

Bravo AF: 0.772

Asia WGS AF: 0.827 AC: 2877 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.49
PhyloP100		-0.64
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: rs11666627; hg19: chr19-19211238;