chr6-46655916-C-T

Variant names:

• chr6-46655916-C-T
• rs186905204
• NM_004277.5:c.180C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_004277.5(SLC25A27):​c.180C>T​(p.Asp60Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0018 in 1,613,496 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0019 (10 hom.)
• Consequence: SLC25A27 NM_004277.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.88
• Publications: 1 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 6-46655916-C-T is Benign according to our data. Variant chr6-46655916-C-T is described in ClinVar as Benign. ClinVar VariationId is 718746.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.88 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 10 AR gene

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.180C>T	p.Asp60Asp	synonymous	Exon 2 of 9	NP_004268.3
	SLC25A27	NM_001204051.2		c.180C>T	p.Asp60Asp	synonymous	Exon 2 of 9	NP_001190980.1	B4DHR4
	SLC25A27	NM_001204052.2		c.180C>T	p.Asp60Asp	synonymous	Exon 2 of 7	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.180C>T	p.Asp60Asp	synonymous	Exon 2 of 9	ENSP00000360398.3	O95847-1
	SLC25A27	ENST00000411689.6	TSL:1	c.180C>T	p.Asp60Asp	synonymous	Exon 2 of 7	ENSP00000412024.2	O95847-2

Frequencies

GnomAD3 genomes AF: 0.00131 AC: 199 AN: 151840 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000847

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000787

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00208

Gnomad FIN AF: 0.000380

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00202

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.00192 AC: 479 AN: 249096 AF XY: 0.00214

Gnomad AFR exome AF: 0.000324

Gnomad AMR exome AF: 0.00253

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.00220

Gnomad OTH exome AF: 0.00347

GnomAD4 exome AF: 0.00185 AC: 2705 AN: 1461538 Hom.: 10 Cov.: 30 AF XY: 0.00193 AC XY: 1400 AN XY: 727078

African (AFR) AF: 0.000449 AC: 15 AN: 33438

American (AMR) AF: 0.00262 AC: 117 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39682

South Asian (SAS) AF: 0.00377 AC: 325 AN: 86216

European-Finnish (FIN) AF: 0.000374 AC: 20 AN: 53410

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5768

European-Non Finnish (NFE) AF: 0.00189 AC: 2106 AN: 1111836

Other (OTH) AF: 0.00177 AC: 107 AN: 60386

GnomAD4 genome AF: 0.00130 AC: 198 AN: 151958 Hom.: 0 Cov.: 30 AF XY: 0.00118 AC XY: 88 AN XY: 74262

African (AFR) AF: 0.000844 AC: 35 AN: 41446

American (AMR) AF: 0.000720 AC: 11 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00208 AC: 10 AN: 4808

European-Finnish (FIN) AF: 0.000380 AC: 4 AN: 10518

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00202 AC: 137 AN: 67980

Other (OTH) AF: 0.000475 AC: 1 AN: 2104

Alfa AF: 0.00149 Hom.: 0

Bravo AF: 0.00125

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00120

EpiControl AF: 0.00190

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	8.5
DANN	Benign	0.83
PhyloP100		-1.9
Mutation Taster		=299/1	polymorphism

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: rs186905204; hg19: chr6-46623653;