rs2270450

Positions:

• chr6-46677138-C-T

Variant summary

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

The NM_004277.5(SLC25A27):​c.*684C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 162,402 control chromosomes in the GnomAD database, including 7,303 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 0.29 (6691 hom., cov: 32)
  • Exomes 𝑓: 0.34 (612 hom.)
• Consequence: SLC25A27 NM_004277.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A27	NM_004277.5	c.*684C>T		3_prime_UTR_variant	9/9	ENST00000371347.10	NP_004268.3
TDRD6-AS1	NR_134643.1	n.233-6553G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A27	ENST00000371347.10	c.*684C>T		3_prime_UTR_variant	9/9	1	NM_004277.5	ENSP00000360398	P1
TDRD6-AS1	ENST00000434329.2	n.233-6553G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44481 AN: 151888 Hom.: 6693 Cov.: 32

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.313

GnomAD4 exome AF: 0.342 AC: 3560 AN: 10396 Hom.: 612 Cov.: 0 AF XY: 0.347 AC XY: 1872 AN XY: 5394

Gnomad4 AFR exome AF: 0.326

Gnomad4 AMR exome AF: 0.379

Gnomad4 ASJ exome AF: 0.358

Gnomad4 EAS exome AF: 0.192

Gnomad4 SAS exome AF: 0.582

Gnomad4 FIN exome AF: 0.326

Gnomad4 NFE exome AF: 0.319

Gnomad4 OTH exome AF: 0.338

GnomAD4 genome AF: 0.293 AC: 44511 AN: 152006 Hom.: 6691 Cov.: 32 AF XY: 0.296 AC XY: 22009 AN XY: 74320

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.353

Gnomad4 ASJ AF: 0.341

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.521

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.281

Gnomad4 OTH AF: 0.317

Alfa AF: 0.292 Hom.: 14274

Bravo AF: 0.287

Asia WGS AF: 0.377 AC: 1311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.67

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: rs2270450; hg19: chr6-46644875;