rs2304075

Positions:

• chr5-135842435-T-C
• chr5-135842435-T-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.66T>C​(p.Val22=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.804 in 1,611,370 control chromosomes in the GnomAD database, including 524,155 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 0.78 (46647 hom., cov: 32)
  • Exomes 𝑓: 0.81 (477508 hom.)
• Consequence: SLC25A48 NM_001349336.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.66

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=-0.77).
• BP7: Synonymous conserved (PhyloP=-2.66 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A48	NM_001349336.2	c.66T>C	p.Val22=	synonymous_variant	2/8	ENST00000681962.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A48	ENST00000681962.1	c.66T>C	p.Val22=	synonymous_variant	2/8		NM_001349336.2	P1

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118755 AN: 152004 Hom.: 46611 Cov.: 32

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.899

Gnomad AMR AF: 0.717

Gnomad ASJ AF: 0.823

Gnomad EAS AF: 0.706

Gnomad SAS AF: 0.783

Gnomad FIN AF: 0.791

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.817

Gnomad OTH AF: 0.805

GnomAD3 exomes AF: 0.764 AC: 190457 AN: 249416 Hom.: 74029 AF XY: 0.774 AC XY: 104813 AN XY: 135338

Gnomad AFR exome AF: 0.748

Gnomad AMR exome AF: 0.563

Gnomad ASJ exome AF: 0.819

Gnomad EAS exome AF: 0.702

Gnomad SAS exome AF: 0.783

Gnomad FIN exome AF: 0.792

Gnomad NFE exome AF: 0.820

Gnomad OTH exome AF: 0.789

GnomAD4 exome AF: 0.807 AC: 1177191 AN: 1459248 Hom.: 477508 Cov.: 48 AF XY: 0.808 AC XY: 586557 AN XY: 726018

Gnomad4 AFR exome AF: 0.739

Gnomad4 AMR exome AF: 0.577

Gnomad4 ASJ exome AF: 0.816

Gnomad4 EAS exome AF: 0.685

Gnomad4 SAS exome AF: 0.785

Gnomad4 FIN exome AF: 0.796

Gnomad4 NFE exome AF: 0.824

Gnomad4 OTH exome AF: 0.809

GnomAD4 genome AF: 0.781 AC: 118841 AN: 152122 Hom.: 46647 Cov.: 32 AF XY: 0.779 AC XY: 57944 AN XY: 74368

Gnomad4 AFR AF: 0.746

Gnomad4 AMR AF: 0.716

Gnomad4 ASJ AF: 0.823

Gnomad4 EAS AF: 0.705

Gnomad4 SAS AF: 0.783

Gnomad4 FIN AF: 0.791

Gnomad4 NFE AF: 0.817

Gnomad4 OTH AF: 0.805

Alfa AF: 0.812 Hom.: 118674

Bravo AF: 0.770

Asia WGS AF: 0.758 AC: 2638 AN: 3478

EpiCase AF: 0.834

EpiControl AF: 0.829

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.2
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs2304075; hg19: chr5-135178124; COSMIC: COSV50849431;