6-46662331-G-A

Variant names:

• chr6-46662331-G-A
• rs9381469
• NM_004277.5:c.384-45G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SLC25A27	NM_004277.5	c.384-45G>A		intron_variant	Intron 3 of 8	ENST00000371347.10	NP_004268.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A27	ENST00000371347.10	c.384-45G>A		intron_variant	Intron 3 of 8	1	NM_004277.5	ENSP00000360398.3

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

GnomAD2 exomes AF: 0.456 AC: 111487 AN: 244736 AF XY: 0.448

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 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

African (AFR) AF: 0.503 AC: 16489 AN: 32786

American (AMR) AF: 0.442 AC: 19366 AN: 43864

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 11404 AN: 25770

East Asian (EAS) AF: 0.515 AC: 20366 AN: 39538

South Asian (SAS) AF: 0.272 AC: 23143 AN: 85032

European-Finnish (FIN) AF: 0.452 AC: 24073 AN: 53254

Middle Eastern (MID) AF: 0.436 AC: 2473 AN: 5678

European-Non Finnish (NFE) AF: 0.496 AC: 541610 AN: 1092410

Other (OTH) AF: 0.479 AC: 28568 AN: 59586

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

African (AFR) AF: 0.507 AC: 21004 AN: 41400

American (AMR) AF: 0.458 AC: 6987 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 1565 AN: 3468

East Asian (EAS) AF: 0.563 AC: 2896 AN: 5144

South Asian (SAS) AF: 0.265 AC: 1279 AN: 4822

European-Finnish (FIN) AF: 0.443 AC: 4666 AN: 10540

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.495 AC: 33638 AN: 67950

Other (OTH) AF: 0.465 AC: 980 AN: 2108

Alfa AF: 0.473 Hom.: 29068

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
PhyloP100		-0.025
PromoterAI		-0.020	Neutral
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: rs9381469; hg19: chr6-46630068; COSMIC: COSV64927889; COSMIC: COSV64927889;