NM_178526.5:c.80A>C

Variant names:

• chr19-19096204-A-C
• rs749095738
• NM_178526.5:c.80A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178526.5(SLC25A42):​c.80A>C​(p.Lys27Thr) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000583 in 1,458,098 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000058 (0 hom.)
• Consequence: SLC25A42 NM_178526.5 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.54
• Publications: 2 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15580356).

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.80A>C	p.Lys27Thr	missense splice_region	Exon 2 of 8	NP_848621.2	Q86VD7
	SLC25A42	NM_001321544.2		c.80A>C	p.Lys27Thr	missense splice_region	Exon 2 of 8	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.80A>C	p.Lys27Thr	missense splice_region	Exon 2 of 8	ENSP00000326693.6	Q86VD7
	SLC25A42	ENST00000857041.1		c.80A>C	p.Lys27Thr	missense splice_region	Exon 2 of 8	ENSP00000527100.1
	SLC25A42	ENST00000857042.1		c.80A>C	p.Lys27Thr	missense splice_region	Exon 3 of 9	ENSP00000527101.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000200 AC: 5 AN: 250404 AF XY: 0.0000369

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000442

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000583 AC: 85 AN: 1458098 Hom.: 0 Cov.: 31 AF XY: 0.0000635 AC XY: 46 AN XY: 724712

African (AFR) AF: 0.00 AC: 0 AN: 32892

American (AMR) AF: 0.00 AC: 0 AN: 44632

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39604

South Asian (SAS) AF: 0.00 AC: 0 AN: 86214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5730

European-Non Finnish (NFE) AF: 0.0000748 AC: 83 AN: 1109422

Other (OTH) AF: 0.0000333 AC: 2 AN: 60132

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000450 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.20
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	1.5	L
PhyloP100		5.5
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.19
Sift	Benign	0.18	T
Sift4G	Benign	0.45	T
Polyphen		0.039	B
Vest4		0.24
MutPred		0.31		Loss of ubiquitination at K27 (P = 0.002)
MVP		0.33
MPC		0.83
ClinPred		0.13	T
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.077
gMVP		0.74
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs749095738; hg19: chr19-19207013; COSMIC: COSV59381563;