rs9381469

Positions:

• chr6-46662331-G-A
• chr6-46662331-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004277.5(SLC25A27):​c.384-45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 1,589,822 control chromosomes in the GnomAD database, including 185,202 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 0.48 (17850 hom., cov: 31)
  • Exomes 𝑓: 0.48 (167352 hom.)
• Consequence: SLC25A27 NM_004277.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0250

Genes affected

SLC25A27 (HGNC:21065): (solute carrier family 25 member 27) Mitochondrial uncoupling proteins (UCP) are members of the larger family of mitochondrial anion carrier proteins (MACP). UCPs separate oxidative phosphorylation from ATP synthesis with energy dissipated as heat, also referred to as the mitochondrial proton leak. UCPs facilitate the transfer of anions from the inner to the outer mitochondrial membrane and the return transfer of protons from the outer to the inner mitochondrial membrane. They also reduce the mitochondrial membrane potential in mammalian cells. Tissue specificity occurs for the different UCPs and the exact methods of how UCPs transfer H+/OH- are not known. UCPs contain the three homologous protein domains of MACPs. Transcripts of this gene are only detected in brain tissue and are specifically modulated by various environmental conditions. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Feb 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A27	NM_004277.5	c.384-45G>A		intron_variant		ENST00000371347.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A27	ENST00000371347.10	c.384-45G>A		intron_variant		1	NM_004277.5	P1
SLC25A27	ENST00000411689.6	c.384-45G>A		intron_variant		1
SLC25A27	ENST00000603486.5	c.174-45G>A		intron_variant		5
SLC25A27	ENST00000604908.1	n.295-45G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73402 AN: 151786 Hom.: 17843 Cov.: 31

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.562

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.469

GnomAD3 exomes AF: 0.456 AC: 111487 AN: 244736 Hom.: 26145 AF XY: 0.448 AC XY: 59429 AN XY: 132798

Gnomad AFR exome AF: 0.506

Gnomad AMR exome AF: 0.442

Gnomad ASJ exome AF: 0.433

Gnomad EAS exome AF: 0.576

Gnomad SAS exome AF: 0.268

Gnomad FIN exome AF: 0.448

Gnomad NFE exome AF: 0.487

Gnomad OTH exome AF: 0.451

GnomAD4 exome AF: 0.478 AC: 687492 AN: 1437918 Hom.: 167352 Cov.: 26 AF XY: 0.472 AC XY: 338408 AN XY: 716352

Gnomad4 AFR exome AF: 0.503

Gnomad4 AMR exome AF: 0.442

Gnomad4 ASJ exome AF: 0.443

Gnomad4 EAS exome AF: 0.515

Gnomad4 SAS exome AF: 0.272

Gnomad4 FIN exome AF: 0.452

Gnomad4 NFE exome AF: 0.496

Gnomad4 OTH exome AF: 0.479

GnomAD4 genome AF: 0.484 AC: 73452 AN: 151904 Hom.: 17850 Cov.: 31 AF XY: 0.480 AC XY: 35642 AN XY: 74218

Gnomad4 AFR AF: 0.507

Gnomad4 AMR AF: 0.458

Gnomad4 ASJ AF: 0.451

Gnomad4 EAS AF: 0.563

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.443

Gnomad4 NFE AF: 0.495

Gnomad4 OTH AF: 0.465

Alfa AF: 0.469 Hom.: 22468

Bravo AF: 0.490

Asia WGS AF: 0.388 AC: 1349 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.45
DANN	Benign	0.34

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

Publications

LitVar

Other links and lift over

dbSNP: rs9381469; hg19: chr6-46630068; COSMIC: COSV64927889; COSMIC: COSV64927889;