rs2067000

Positions:

• chr5-135671865-A-C
• chr5-135671865-A-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2 BP4_Strong BS1

The NM_001349335.2(SLC25A48):​c.-521+36909A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.025 in 126,826 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.025 (0 hom., cov: 21)
  • Failed GnomAD Quality Control
• Consequence: SLC25A48 NM_001349335.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.878

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 Likely_benign. Variant got -6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.025 (3174/126826) while in subpopulation NFE AF= 0.0273 (1619/59254). AF 95% confidence interval is 0.0262. There are 0 homozygotes in gnomad4. There are 1484 alleles in male gnomad4 subpopulation. Median coverage is 21. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A48	NM_001349335.2	c.-521+36909A>C		intron_variant
SLC25A48	NM_001349345.2	c.-521+36909A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A48	ENST00000646290.1	c.-521+36909A>C		intron_variant
SLC25A48	ENST00000647391.1	n.829+118A>C		intron_variant, non_coding_transcript_variant
SLC25A48	ENST00000698885.1	n.365-89159A>C		intron_variant, non_coding_transcript_variant
SLC25A48	ENST00000698886.1	n.751+36909A>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0250 AC: 3171 AN: 126746 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.0264

Gnomad AMI AF: 0.0223

Gnomad AMR AF: 0.0213

Gnomad ASJ AF: 0.0259

Gnomad EAS AF: 0.0250

Gnomad SAS AF: 0.0258

Gnomad FIN AF: 0.00855

Gnomad MID AF: 0.00690

Gnomad NFE AF: 0.0273

Gnomad OTH AF: 0.0249

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

GnomAD4 genome AF: 0.0250 AC: 3174 AN: 126826 Hom.: 0 Cov.: 21 AF XY: 0.0242 AC XY: 1484 AN XY: 61328

Gnomad4 AFR AF: 0.0265

Gnomad4 AMR AF: 0.0213

Gnomad4 ASJ AF: 0.0259

Gnomad4 EAS AF: 0.0250

Gnomad4 SAS AF: 0.0257

Gnomad4 FIN AF: 0.00855

Gnomad4 NFE AF: 0.0273

Gnomad4 OTH AF: 0.0247

Alfa AF: 0.00486 Hom.: 12691

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.48
DANN	Benign	0.33

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2067000; hg19: chr5-135007554;