rs6596270

Variant names:

• chr5-135842453-A-G
• rs6596270
• NM_001349336.2:c.84A>G
• SLC25A48 p.Thr28Thr

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.84A>G​(p.Thr28Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,608,836 control chromosomes in the GnomAD database, including 32,154 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.19 (2801 hom., cov: 33)
  • Exomes 𝑓: 0.19 (29353 hom.)
• Consequence: SLC25A48 NM_001349336.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• Publications: 16 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=-0.61).
• BP7: Synonymous conserved (PhyloP=-1.37 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.207 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.84A>G	p.Thr28Thr	synonymous	Exon 2 of 8	NP_001336265.1	Q6ZT89-1
	SLC25A48	NM_145282.5		c.84A>G	p.Thr28Thr	synonymous	Exon 2 of 5	NP_660325.4	Q6ZT89-3
	SLC25A48	NM_001349335.2		c.-79A>G		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.84A>G	p.Thr28Thr	synonymous	Exon 2 of 8	ENSP00000506858.1	Q6ZT89-1
	SLC25A48	ENST00000412661.3	TSL:1	c.84A>G	p.Thr28Thr	synonymous	Exon 2 of 5	ENSP00000413049.2	Q6ZT89-3
	SLC25A48	ENST00000650267.1		c.84A>G	p.Thr28Thr	synonymous	Exon 2 of 9	ENSP00000497060.1	A0A3B3IS12

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28383 AN: 152098 Hom.: 2797 Cov.: 33

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.0117

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.199

GnomAD2 exomes AF: 0.170 AC: 42451 AN: 249400 AF XY: 0.172

Gnomad AFR exome AF: 0.180

Gnomad AMR exome AF: 0.113

Gnomad ASJ exome AF: 0.250

Gnomad EAS exome AF: 0.00712

Gnomad FIN exome AF: 0.210

Gnomad NFE exome AF: 0.208

Gnomad OTH exome AF: 0.190

GnomAD4 exome AF: 0.195 AC: 283840 AN: 1456620 Hom.: 29353 Cov.: 33 AF XY: 0.194 AC XY: 140530 AN XY: 724814

African (AFR) AF: 0.178 AC: 5924 AN: 33370

American (AMR) AF: 0.118 AC: 5261 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 6359 AN: 26086

East Asian (EAS) AF: 0.0210 AC: 833 AN: 39690

South Asian (SAS) AF: 0.129 AC: 11113 AN: 86132

European-Finnish (FIN) AF: 0.212 AC: 11295 AN: 53374

Middle Eastern (MID) AF: 0.219 AC: 1258 AN: 5734

European-Non Finnish (NFE) AF: 0.208 AC: 230381 AN: 1107378

Other (OTH) AF: 0.190 AC: 11416 AN: 60170

GnomAD4 genome AF: 0.187 AC: 28404 AN: 152216 Hom.: 2801 Cov.: 33 AF XY: 0.183 AC XY: 13655 AN XY: 74414

African (AFR) AF: 0.181 AC: 7528 AN: 41528

American (AMR) AF: 0.150 AC: 2288 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 863 AN: 3472

East Asian (EAS) AF: 0.0118 AC: 61 AN: 5182

South Asian (SAS) AF: 0.122 AC: 587 AN: 4820

European-Finnish (FIN) AF: 0.203 AC: 2159 AN: 10610

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14270 AN: 67988

Other (OTH) AF: 0.197 AC: 416 AN: 2112

Alfa AF: 0.204 Hom.: 5573

Bravo AF: 0.181

Asia WGS AF: 0.0810 AC: 281 AN: 3478

EpiCase AF: 0.221

EpiControl AF: 0.214

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_noAF	Benign	-0.61
CADD	Benign	1.0
DANN	Benign	0.73
PhyloP100		-1.4
Mutation Taster		=99/1	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: rs6596270;

hg19: chr5-135178142;

COSMIC: COSV50848337;