NM_178526.5:c.*385C>G

Variant names:

• chr19-19111261-C-G
• rs10417974
• NM_178526.5:c.*385C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_178526.5(SLC25A42):​c.*385C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,076 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC25A42 NM_178526.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.808
• Publications: 11 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A42	NM_178526.5	c.*385C>G		3_prime_UTR_variant	Exon 8 of 8	ENST00000318596.8	NP_848621.2
SLC25A42	NM_001321544.2	c.*385C>G		3_prime_UTR_variant	Exon 8 of 8		NP_001308473.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A42	ENST00000318596.8	c.*385C>G		3_prime_UTR_variant	Exon 8 of 8	1	NM_178526.5	ENSP00000326693.6

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152076 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 90278 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 48160

African (AFR) AF: 0.00 AC: 0 AN: 1438

American (AMR) AF: 0.00 AC: 0 AN: 4056

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2274

East Asian (EAS) AF: 0.00 AC: 0 AN: 2386

South Asian (SAS) AF: 0.00 AC: 0 AN: 14508

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 394

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 55852

Other (OTH) AF: 0.00 AC: 0 AN: 4954

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152076 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74292

African (AFR) AF: 0.0000242 AC: 1 AN: 41400

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 21780

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.090
DANN	Benign	0.67
PhyloP100		-0.81

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: rs10417974; hg19: chr19-19222070;