6-46673255-C-G

Variant names:

• chr6-46673255-C-G
• rs9472817
• NM_004277.5:c.900+2027C>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.900+2027C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 152,086 control chromosomes in the GnomAD database, including 13,765 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 0.42 (13765 hom., cov: 32)
• Consequence: SLC25A27 NM_004277.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.166
• Publications: 12 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]

TDRD6-AS1 (HGNC:56119): (TDRD6 and SLC25A27 antisense RNA 1)

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004277.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A27	NM_004277.5	MANE Select	c.900+2027C>G		intron	N/A	NP_004268.3
	SLC25A27	NM_001204051.2		c.900+2027C>G		intron	N/A	NP_001190980.1	B4DHR4
	SLC25A27	NM_001204052.2		c.705-3392C>G		intron	N/A	NP_001190981.1	O95847-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A27	ENST00000371347.10	TSL:1 MANE Select	c.900+2027C>G		intron	N/A	ENSP00000360398.3	O95847-1
	SLC25A27	ENST00000411689.6	TSL:1	c.705-3392C>G		intron	N/A	ENSP00000412024.2	O95847-2
	SLC25A27	ENST00000604616.1	TSL:5	c.291+2027C>G		intron	N/A	ENSP00000473804.1	S4R300

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63727 AN: 151968 Hom.: 13765 Cov.: 32

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.418

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

GnomAD4 genome AF: 0.419 AC: 63748 AN: 152086 Hom.: 13765 Cov.: 32 AF XY: 0.417 AC XY: 30967 AN XY: 74330

African (AFR) AF: 0.331 AC: 13717 AN: 41500

American (AMR) AF: 0.422 AC: 6440 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1426 AN: 3472

East Asian (EAS) AF: 0.564 AC: 2916 AN: 5170

South Asian (SAS) AF: 0.232 AC: 1116 AN: 4820

European-Finnish (FIN) AF: 0.430 AC: 4539 AN: 10548

Middle Eastern (MID) AF: 0.394 AC: 115 AN: 292

European-Non Finnish (NFE) AF: 0.475 AC: 32310 AN: 67992

Other (OTH) AF: 0.415 AC: 873 AN: 2106

Alfa AF: 0.309 Hom.: 830

Bravo AF: 0.419

Asia WGS AF: 0.359 AC: 1246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.43
PhyloP100		0.17
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: rs9472817; hg19: chr6-46640992; COSMIC: COSV64928719; COSMIC: COSV64928719;