5-135875777-C-T

Variant names:

• chr5-135875777-C-T
• rs7717673
• NM_001349336.2:c.813+1623C>T

Variant summary

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

The NM_001349336.2(SLC25A48):​c.813+1623C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,182 control chromosomes in the GnomAD database, including 5,168 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 0.20 (5168 hom., cov: 32)
  • Exomes 𝑓: 0.036 (0 hom.)
• Consequence: SLC25A48 NM_001349336.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.60
• Publications: 5 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 (AFR) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A48	NM_001349336.2	c.813+1623C>T		intron_variant	Intron 6 of 7	ENST00000681962.1	NP_001336265.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A48	ENST00000681962.1	c.813+1623C>T		intron_variant	Intron 6 of 7		NM_001349336.2	ENSP00000506858.1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30187 AN: 152036 Hom.: 5146 Cov.: 32

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.0110

Gnomad SAS AF: 0.0528

Gnomad FIN AF: 0.0889

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0995

Gnomad OTH AF: 0.184

GnomAD4 exome AF: 0.0357 AC: 1 AN: 28 Hom.: 0 Cov.: 0 AF XY: 0.0500 AC XY: 1 AN XY: 20

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0500 AC: 1 AN: 20

Other (OTH) AF: 0.00 AC: 0 AN: 2

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.199 AC: 30250 AN: 152154 Hom.: 5168 Cov.: 32 AF XY: 0.193 AC XY: 14350 AN XY: 74404

African (AFR) AF: 0.463 AC: 19192 AN: 41472

American (AMR) AF: 0.122 AC: 1863 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 737 AN: 3472

East Asian (EAS) AF: 0.0110 AC: 57 AN: 5184

South Asian (SAS) AF: 0.0527 AC: 254 AN: 4824

European-Finnish (FIN) AF: 0.0889 AC: 942 AN: 10600

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0995 AC: 6767 AN: 67986

Other (OTH) AF: 0.183 AC: 386 AN: 2112

Alfa AF: 0.129 Hom.: 8571

Bravo AF: 0.214

Asia WGS AF: 0.0680 AC: 236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.098
DANN	Benign	0.32
PhyloP100		-2.6
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: rs7717673; hg19: chr5-135211466;