rs4246802

Variant names:

• chr5-135864020-A-C
• rs4246802
• NM_001349336.2:c.422-7441A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001349336.2(SLC25A48):​c.422-7441A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.798 in 152,090 control chromosomes in the GnomAD database, including 48,586 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 0.80 (48586 hom., cov: 32)
• Consequence: SLC25A48 NM_001349336.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.917
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.833 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.422-7441A>C		intron	N/A	NP_001336265.1	Q6ZT89-1
	SLC25A48	NM_001349335.2		c.260-7441A>C		intron	N/A	NP_001336264.1	J3KQI1
	SLC25A48	NM_001349345.2		c.259+11199A>C		intron	N/A	NP_001336274.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A48	ENST00000681962.1	MANE Select	c.422-7441A>C		intron	N/A	ENSP00000506858.1	Q6ZT89-1
	SLC25A48	ENST00000412661.3	TSL:1	c.421+11199A>C		intron	N/A	ENSP00000413049.2	Q6ZT89-3
	SLC25A48	ENST00000650267.1		c.422-7441A>C		intron	N/A	ENSP00000497060.1	A0A3B3IS12

Frequencies

GnomAD3 genomes AF: 0.798 AC: 121229 AN: 151972 Hom.: 48545 Cov.: 32

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.909

Gnomad AMR AF: 0.790

Gnomad ASJ AF: 0.824

Gnomad EAS AF: 0.699

Gnomad SAS AF: 0.813

Gnomad FIN AF: 0.769

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.839

Gnomad OTH AF: 0.824

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.798 AC: 121328 AN: 152090 Hom.: 48586 Cov.: 32 AF XY: 0.794 AC XY: 59033 AN XY: 74356

African (AFR) AF: 0.744 AC: 30825 AN: 41454

American (AMR) AF: 0.790 AC: 12080 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.824 AC: 2858 AN: 3470

East Asian (EAS) AF: 0.699 AC: 3602 AN: 5152

South Asian (SAS) AF: 0.813 AC: 3924 AN: 4826

European-Finnish (FIN) AF: 0.769 AC: 8135 AN: 10574

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.839 AC: 57075 AN: 68006

Other (OTH) AF: 0.823 AC: 1739 AN: 2112

Alfa AF: 0.831 Hom.: 96602

Bravo AF: 0.795

Asia WGS AF: 0.770 AC: 2680 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.31
PhyloP100		-0.92
Mutation Taster		=100/0	polymorphism (auto)

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

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

Other links and lift over

dbSNP: rs4246802;

hg19: chr5-135199709;

COSMIC: COSV50848421;