rs6901132

Variant names:

• chr6-46664064-A-G
• rs6901132
• NM_004277.5:c.507-710A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-46664064-A-G
• chr6-46664064-A-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.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
• Publications: 8 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=-0.64).
• 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 rank	MANE	Protein	UniProt
SLC25A27	NM_004277.5	c.507-710A>G		intron_variant	Intron 4 of 8	ENST00000371347.10	NP_004268.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A27	ENST00000371347.10	c.507-710A>G		intron_variant	Intron 4 of 8	1	NM_004277.5	ENSP00000360398.3

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

African (AFR) AF: 0.389 AC: 16096 AN: 41412

American (AMR) AF: 0.392 AC: 5991 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1328 AN: 3472

East Asian (EAS) AF: 0.321 AC: 1662 AN: 5174

South Asian (SAS) AF: 0.625 AC: 3012 AN: 4822

European-Finnish (FIN) AF: 0.328 AC: 3464 AN: 10548

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.324 AC: 21987 AN: 67940

Other (OTH) AF: 0.377 AC: 796 AN: 2110

Alfa AF: 0.343 Hom.: 7423

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
PhyloP100		-0.19
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: rs6901132; hg19: chr6-46631801;