chr6-46664149-A-G

Position:

• chr6-46664149-A-G

Variant summary

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

The ENST00000371347.10(SLC25A27):​c.507-625A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.853 in 152,192 control chromosomes in the GnomAD database, including 55,768 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 0.85 (55768 hom., cov: 33)
• Consequence: SLC25A27 ENST00000371347.10 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A27	NM_004277.5	c.507-625A>G		intron_variant		ENST00000371347.10	NP_004268.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A27	ENST00000371347.10	c.507-625A>G		intron_variant		1	NM_004277.5	ENSP00000360398	P1

Frequencies

GnomAD3 genomes AF: 0.853 AC: 129703 AN: 152074 Hom.: 55710 Cov.: 33

Gnomad AFR AF: 0.954

Gnomad AMI AF: 0.614

Gnomad AMR AF: 0.852

Gnomad ASJ AF: 0.823

Gnomad EAS AF: 0.886

Gnomad SAS AF: 0.891

Gnomad FIN AF: 0.763

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.805

Gnomad OTH AF: 0.842

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

GnomAD4 genome AF: 0.853 AC: 129820 AN: 152192 Hom.: 55768 Cov.: 33 AF XY: 0.853 AC XY: 63435 AN XY: 74384

Gnomad4 AFR AF: 0.954

Gnomad4 AMR AF: 0.852

Gnomad4 ASJ AF: 0.823

Gnomad4 EAS AF: 0.886

Gnomad4 SAS AF: 0.891

Gnomad4 FIN AF: 0.763

Gnomad4 NFE AF: 0.805

Gnomad4 OTH AF: 0.842

Alfa AF: 0.821 Hom.: 33061

Bravo AF: 0.857

Asia WGS AF: 0.901 AC: 3134 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	0.26
DANN	Benign	0.61

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: rs6901178; hg19: chr6-46631886;