rs6901132

chr6-46664064-A-Gchr6-46664064-A-T

Variant summary

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

The NM_004277.5(SLC25A27):c.507-710A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 151,958 control chromosomes in the GnomAD database, including 10,024 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 0.36 (10024 hom., cov: 32)
• Consequence: SLC25A27 NM_004277.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.188

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=-0.64).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A27	NM_004277.5	c.507-710A>G		intron_variant		ENST00000371347.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A27	ENST00000371347.10	c.507-710A>G		intron_variant		1	NM_004277.5	P1

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54674 AN: 151840 Hom.: 10027 Cov.: 32

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.625

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.373

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

GnomAD4 genome AF: 0.360 AC: 54716 AN: 151958 Hom.: 10024 Cov.: 32 AF XY: 0.363 AC XY: 26971 AN XY: 74294

Gnomad4 AFR AF: 0.389

Gnomad4 AMR AF: 0.392

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.321

Gnomad4 SAS AF: 0.625

Gnomad4 FIN AF: 0.328

Gnomad4 NFE AF: 0.324

Gnomad4 OTH AF: 0.377

Alfa AF: 0.349 Hom.: 5386

Bravo AF: 0.355

Asia WGS AF: 0.502 AC: 1745 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	12
Dann	Benign	0.91

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: rs6901132; hg19: chr6-46631801;