rs2304075

Variant names:

• chr5-135842435-T-C
• rs2304075
• NM_001349336.2:c.66T>C
• SLC25A48 p.Val22Val

Your query was ambiguous. Multiple possible variants found:

• chr5-135842435-T-C
• chr5-135842435-T-G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001349336.2(SLC25A48):​c.66T>C​(p.Val22Val) 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
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349336.2. 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
	SLC25A48	NM_001349336.2	MANE Select	c.66T>C	p.Val22Val	synonymous	Exon 2 of 8	NP_001336265.1	Q6ZT89-1
	SLC25A48	NM_145282.5		c.66T>C	p.Val22Val	synonymous	Exon 2 of 5	NP_660325.4	Q6ZT89-3
	SLC25A48	NM_001349335.2		c.-97T>C		5_prime_UTR	Exon 5 of 11	NP_001336264.1	J3KQI1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A48	ENST00000681962.1	MANE Select	c.66T>C	p.Val22Val	synonymous	Exon 2 of 8	ENSP00000506858.1	Q6ZT89-1
	SLC25A48	ENST00000412661.3	TSL:1	c.66T>C	p.Val22Val	synonymous	Exon 2 of 5	ENSP00000413049.2	Q6ZT89-3
	SLC25A48	ENST00000650267.1		c.66T>C	p.Val22Val	synonymous	Exon 2 of 9	ENSP00000497060.1	A0A3B3IS12

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

GnomAD2 exomes AF: 0.764 AC: 190457 AN: 249416 AF XY: 0.774

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 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

African (AFR) AF: 0.739 AC: 24698 AN: 33412

American (AMR) AF: 0.577 AC: 25764 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.816 AC: 21307 AN: 26114

East Asian (EAS) AF: 0.685 AC: 27198 AN: 39692

South Asian (SAS) AF: 0.785 AC: 67668 AN: 86178

European-Finnish (FIN) AF: 0.796 AC: 42518 AN: 53392

Middle Eastern (MID) AF: 0.880 AC: 5058 AN: 5746

European-Non Finnish (NFE) AF: 0.824 AC: 914226 AN: 1109760

Other (OTH) AF: 0.809 AC: 48754 AN: 60270

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

African (AFR) AF: 0.746 AC: 30971 AN: 41494

American (AMR) AF: 0.716 AC: 10954 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.823 AC: 2855 AN: 3470

East Asian (EAS) AF: 0.705 AC: 3644 AN: 5168

South Asian (SAS) AF: 0.783 AC: 3773 AN: 4820

European-Finnish (FIN) AF: 0.791 AC: 8362 AN: 10578

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.817 AC: 55506 AN: 67974

Other (OTH) AF: 0.805 AC: 1701 AN: 2114

Alfa AF: 0.806 Hom.: 232077

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.2
DANN	Benign	0.67
PhyloP100		-2.7
Mutation Taster		=298/2	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2304075;

hg19: chr5-135178124;

COSMIC: COSV50849431;