5-135846434-A-G

Variant names:

• chr5-135846434-A-G
• rs4976493
• NM_001349336.2:c.90+3975A>G

Variant summary

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

The NM_001349336.2(SLC25A48):​c.90+3975A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 152,008 control chromosomes in the GnomAD database, including 30,777 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 0.63 (30777 hom., cov: 32)
• Consequence: SLC25A48 NM_001349336.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.234
• Publications: 4 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=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.686 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A48	NM_001349336.2	MANE Select	c.90+3975A>G		intron	N/A	NP_001336265.1
	SLC25A48	NM_001349335.2		c.-73+3975A>G		intron	N/A	NP_001336264.1
	SLC25A48	NM_001349345.2		c.-73+3975A>G		intron	N/A	NP_001336274.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A48	ENST00000681962.1	MANE Select	c.90+3975A>G		intron	N/A	ENSP00000506858.1
	SLC25A48	ENST00000412661.3	TSL:1	c.90+3975A>G		intron	N/A	ENSP00000413049.2
	SLC25A48	ENST00000650267.1		c.90+3975A>G		intron	N/A	ENSP00000497060.1

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96379 AN: 151890 Hom.: 30737 Cov.: 32

Gnomad AFR AF: 0.675

Gnomad AMI AF: 0.735

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.703

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.638

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

GnomAD4 genome AF: 0.635 AC: 96471 AN: 152008 Hom.: 30777 Cov.: 32 AF XY: 0.635 AC XY: 47162 AN XY: 74298

African (AFR) AF: 0.675 AC: 28000 AN: 41452

American (AMR) AF: 0.583 AC: 8915 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 2110 AN: 3468

East Asian (EAS) AF: 0.703 AC: 3614 AN: 5142

South Asian (SAS) AF: 0.706 AC: 3389 AN: 4800

European-Finnish (FIN) AF: 0.593 AC: 6269 AN: 10566

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.617 AC: 41963 AN: 67966

Other (OTH) AF: 0.640 AC: 1352 AN: 2114

Alfa AF: 0.626 Hom.: 122822

Bravo AF: 0.632

Asia WGS AF: 0.711 AC: 2472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.8
DANN	Benign	0.70
PhyloP100		-0.23
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

Other links and lift over

dbSNP: rs4976493; hg19: chr5-135182123;