chr6-46662104-A-G

Variant names:

• chr6-46662104-A-G
• rs9296505
• NM_004277.5:c.384-272A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004277.5(SLC25A27):​c.384-272A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 152,004 control chromosomes in the GnomAD database, including 17,874 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 (17874 hom., cov: 31)
• Consequence: SLC25A27 NM_004277.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.213
• Publications: 9 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A27	NM_004277.5	c.384-272A>G		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.384-272A>G		intron_variant	Intron 3 of 8	1	NM_004277.5	ENSP00000360398.3
SLC25A27	ENST00000411689.6	c.384-272A>G		intron_variant	Intron 3 of 6	1		ENSP00000412024.2
SLC25A27	ENST00000603486.5	c.174-272A>G		intron_variant	Intron 1 of 3	5		ENSP00000474781.1
SLC25A27	ENST00000604908.1	n.295-272A>G		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73442 AN: 151886 Hom.: 17867 Cov.: 31

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.483 AC: 73492 AN: 152004 Hom.: 17874 Cov.: 31 AF XY: 0.480 AC XY: 35674 AN XY: 74312

African (AFR) AF: 0.507 AC: 21028 AN: 41442

American (AMR) AF: 0.459 AC: 7010 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1562 AN: 3468

East Asian (EAS) AF: 0.564 AC: 2906 AN: 5154

South Asian (SAS) AF: 0.266 AC: 1277 AN: 4808

European-Finnish (FIN) AF: 0.442 AC: 4666 AN: 10568

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

European-Non Finnish (NFE) AF: 0.495 AC: 33629 AN: 67960

Other (OTH) AF: 0.463 AC: 977 AN: 2110

Alfa AF: 0.490 Hom.: 3200

Bravo AF: 0.490

Asia WGS AF: 0.388 AC: 1350 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.8
DANN	Benign	0.65
PhyloP100		0.21
PromoterAI		0.013	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: rs9296505; hg19: chr6-46629841;