6-46658149-C-T

Position:

• chr6-46658149-C-T

Variant summary

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

The NM_004277.5(SLC25A27):​c.299-813C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 152,022 control chromosomes in the GnomAD database, including 10,827 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 0.37 (10827 hom., cov: 33)
• Consequence: SLC25A27 NM_004277.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.162

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A27	NM_004277.5	c.299-813C>T		intron_variant		ENST00000371347.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A27	ENST00000371347.10	c.299-813C>T		intron_variant		1	NM_004277.5	P1
SLC25A27	ENST00000411689.6	c.299-813C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56606 AN: 151904 Hom.: 10821 Cov.: 33

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.382

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

GnomAD4 genome AF: 0.373 AC: 56666 AN: 152022 Hom.: 10827 Cov.: 33 AF XY: 0.375 AC XY: 27875 AN XY: 74316

Gnomad4 AFR AF: 0.432

Gnomad4 AMR AF: 0.401

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.321

Gnomad4 SAS AF: 0.626

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.324

Gnomad4 OTH AF: 0.386

Alfa AF: 0.198 Hom.: 383

Bravo AF: 0.370

Asia WGS AF: 0.505 AC: 1756 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.7
DANN	Benign	0.48

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: rs6907892; hg19: chr6-46625886;