3-48898785-G-T

Position:

• chr3-48898785-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000387.6(SLC25A20):​c.10C>A​(p.Gln4Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC25A20 NM_000387.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.440

Genes affected

SLC25A20 (HGNC:1421): (solute carrier family 25 member 20) This gene product is one of several closely related mitochondrial-membrane carrier proteins that shuttle substrates between cytosol and the intramitochondrial matrix space. This protein mediates the transport of acylcarnitines into mitochondrial matrix for their oxidation by the mitochondrial fatty acid-oxidation pathway. Mutations in this gene are associated with carnitine-acylcarnitine translocase deficiency, which can cause a variety of pathological conditions such as hypoglycemia, cardiac arrest, hepatomegaly, hepatic dysfunction and muscle weakness, and is usually lethal in new born and infants. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06749293).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A20	NM_000387.6	c.10C>A	p.Gln4Lys	missense_variant	1/9	ENST00000319017.5	NP_000378.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A20	ENST00000319017.5	c.10C>A	p.Gln4Lys	missense_variant	1/9	1	NM_000387.6	ENSP00000326305.4
SLC25A20	ENST00000430379.5	c.10C>A	p.Gln4Lys	missense_variant	1/7	3		ENSP00000388986.1
SLC25A20	ENST00000440964.1	n.10C>A		non_coding_transcript_exon_variant	1/10	2		ENSP00000388563.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1421008 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 703284

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	6.1
DANN	Benign	0.91
DEOGEN2	Benign	0.097	.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.67	T;T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.067	T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	-0.17	.;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.030	N;N
REVEL	Benign	0.16
Sift	Benign	0.67	T;T
Sift4G	Benign	0.85	T;T
Polyphen		0.0030	B;B
Vest4		0.12
MutPred		0.29		Gain of methylation at Q4 (P = 0.0042);Gain of methylation at Q4 (P = 0.0042);
MVP		0.85
MPC		0.34
ClinPred		0.032	T
GERP RS		-4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.067
gMVP		0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs756998699; hg19: chr3-48936218;