chr14-100302826-C-T

Variant names:

• chr14-100302826-C-T
• rs1059264
• NM_001039355.3:c.34+3373G>A

Variant summary

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

The NM_001352821.2(SLC25A29):​c.34+3373G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 150,606 control chromosomes in the GnomAD database, including 6,586 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 0.28 (6586 hom., cov: 29)
• Consequence: SLC25A29 NM_001352821.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.302
• Publications: 28 publications found

Genes affected

SLC25A29 (HGNC:20116): (solute carrier family 25 member 29) This gene encodes a nuclear-encoded mitochondrial protein that is a member of the large family of solute carrier family 25 (SLC25) mitochondrial transporters. The members of this superfamily are involved in numerous metabolic pathways and cell functions. This gene product was previously reported to be a mitochondrial carnitine-acylcarnitine-like (CACL) translocase (PMID:128829710) or an ornithine transporter (designated ORNT3, PMID:19287344), however, a recent study characterized the main role of this protein as a mitochondrial transporter of basic amino acids, with a preference for arginine and lysine (PMID:24652292). Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Apr 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001352821.2. 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
	SLC25A29	NM_001039355.3	MANE Select	c.34+3373G>A		intron	N/A	NP_001034444.1
	SLC25A29	NM_001352821.2		c.34+3373G>A		intron	N/A	NP_001339750.1
	SLC25A29	NM_001291813.2		c.-533+3373G>A		intron	N/A	NP_001278742.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A29	ENST00000359232.8	TSL:1 MANE Select	c.34+3373G>A		intron	N/A	ENSP00000352167.3
	SLC25A29	ENST00000392908.7	TSL:2	c.34+3373G>A		intron	N/A	ENSP00000376640.3
	SLC25A29	ENST00000554060.1	TSL:2	c.34+3373G>A		intron	N/A	ENSP00000451644.1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 42844 AN: 150494 Hom.: 6584 Cov.: 29

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.285 AC: 42854 AN: 150606 Hom.: 6586 Cov.: 29 AF XY: 0.286 AC XY: 20968 AN XY: 73368

African (AFR) AF: 0.179 AC: 7337 AN: 40892

American (AMR) AF: 0.273 AC: 4125 AN: 15124

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1335 AN: 3464

East Asian (EAS) AF: 0.177 AC: 912 AN: 5146

South Asian (SAS) AF: 0.348 AC: 1658 AN: 4766

European-Finnish (FIN) AF: 0.354 AC: 3593 AN: 10162

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.336 AC: 22751 AN: 67768

Other (OTH) AF: 0.309 AC: 644 AN: 2086

Alfa AF: 0.316 Hom.: 21712

Bravo AF: 0.271

Asia WGS AF: 0.236 AC: 821 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.6
DANN	Benign	0.58
PhyloP100		0.30
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: rs1059264; hg19: chr14-100769163;