rs10807344

chr6-46657898-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.299-1064C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,132 control chromosomes in the GnomAD database, including 2,743 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 0.17 (2743 hom., cov: 32)
• Consequence: SLC25A27 NM_004277.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0590

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 (SAS) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC25A27	NM_004277.5	c.299-1064C>T		intron_variant		ENST00000371347.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC25A27	ENST00000371347.10	c.299-1064C>T		intron_variant		1	NM_004277.5	P1
SLC25A27	ENST00000411689.6	c.299-1064C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25779 AN: 152012 Hom.: 2741 Cov.: 32

Gnomad AFR AF: 0.0502

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.169 AC: 25780 AN: 152132 Hom.: 2743 Cov.: 32 AF XY: 0.170 AC XY: 12646 AN XY: 74374

Gnomad4 AFR AF: 0.0501

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.132

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.188

Alfa AF: 0.211 Hom.: 3555

Bravo AF: 0.153

Asia WGS AF: 0.171 AC: 596 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	3.3
Dann	Benign	0.55

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: rs10807344; hg19: chr6-46625635;