rs6596270

Positions:

• chr5-135842453-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001349336.2(SLC25A48):​c.84A>G​(p.Thr28=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,608,836 control chromosomes in the GnomAD database, including 32,154 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 0.19 (2801 hom., cov: 33)
  • Exomes 𝑓: 0.19 (29353 hom.)
• Consequence: SLC25A48 NM_001349336.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37

Genes affected

SLC25A48 (HGNC:30451): (solute carrier family 25 member 48) Predicted to enable acyl carnitine transmembrane transporter activity. Predicted to be involved in acyl carnitine transport and amino acid transport. Predicted to be located in mitochondrial inner membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=-1.37 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A48	NM_001349336.2	c.84A>G	p.Thr28=	synonymous_variant	2/8	ENST00000681962.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A48	ENST00000681962.1	c.84A>G	p.Thr28=	synonymous_variant	2/8		NM_001349336.2	P1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28383 AN: 152098 Hom.: 2797 Cov.: 33

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.0117

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.199

GnomAD3 exomes AF: 0.170 AC: 42451 AN: 249400 Hom.: 4191 AF XY: 0.172 AC XY: 23300 AN XY: 135314

Gnomad AFR exome AF: 0.180

Gnomad AMR exome AF: 0.113

Gnomad ASJ exome AF: 0.250

Gnomad EAS exome AF: 0.00712

Gnomad SAS exome AF: 0.127

Gnomad FIN exome AF: 0.210

Gnomad NFE exome AF: 0.208

Gnomad OTH exome AF: 0.190

GnomAD4 exome AF: 0.195 AC: 283840 AN: 1456620 Hom.: 29353 Cov.: 33 AF XY: 0.194 AC XY: 140530 AN XY: 724814

Gnomad4 AFR exome AF: 0.178

Gnomad4 AMR exome AF: 0.118

Gnomad4 ASJ exome AF: 0.244

Gnomad4 EAS exome AF: 0.0210

Gnomad4 SAS exome AF: 0.129

Gnomad4 FIN exome AF: 0.212

Gnomad4 NFE exome AF: 0.208

Gnomad4 OTH exome AF: 0.190

GnomAD4 genome AF: 0.187 AC: 28404 AN: 152216 Hom.: 2801 Cov.: 33 AF XY: 0.183 AC XY: 13655 AN XY: 74414

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.0118

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.197

Alfa AF: 0.208 Hom.: 4431

Bravo AF: 0.181

Asia WGS AF: 0.0810 AC: 281 AN: 3478

EpiCase AF: 0.221

EpiControl AF: 0.214

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	1.0
DANN	Benign	0.73

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: rs6596270; hg19: chr5-135178142; COSMIC: COSV50848337;