rs10807344

Variant names:

• chr6-46657898-C-T
• rs10807344
• NM_004277.5:c.299-1064C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 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 (SAS) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A27	NM_004277.5	c.299-1064C>T		intron_variant	Intron 2 of 8	ENST00000371347.10	NP_004268.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A27	ENST00000371347.10	c.299-1064C>T		intron_variant	Intron 2 of 8	1	NM_004277.5	ENSP00000360398.3
SLC25A27	ENST00000411689.6	c.299-1064C>T		intron_variant	Intron 2 of 6	1		ENSP00000412024.2

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

African (AFR) AF: 0.0501 AC: 2082 AN: 41524

American (AMR) AF: 0.145 AC: 2222 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 992 AN: 3470

East Asian (EAS) AF: 0.132 AC: 682 AN: 5160

South Asian (SAS) AF: 0.282 AC: 1360 AN: 4818

European-Finnish (FIN) AF: 0.227 AC: 2398 AN: 10566

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.226 AC: 15383 AN: 67984

Other (OTH) AF: 0.188 AC: 396 AN: 2108

Alfa AF: 0.201 Hom.: 9221

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
PhyloP100		0.059
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: rs10807344; hg19: chr6-46625635;