rs201819031

Variant names:

• chr6-46664787-C-A
• rs201819031
• NM_004277.5:c.520C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-46664787-C-A
• chr6-46664787-C-G
• chr6-46664787-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004277.5(SLC25A27):​c.520C>A​(p.His174Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000691 in 1,447,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H174Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SLC25A27 NM_004277.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.13
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.520C>A	p.His174Asn	missense	Exon 5 of 9	NP_004268.3
	SLC25A27	NM_001204051.2		c.520C>A	p.His174Asn	missense	Exon 5 of 9	NP_001190980.1	B4DHR4
	SLC25A27	NM_001204052.2		c.520C>A	p.His174Asn	missense	Exon 5 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.520C>A	p.His174Asn	missense	Exon 5 of 9	ENSP00000360398.3	O95847-1
	SLC25A27	ENST00000411689.6	TSL:1	c.520C>A	p.His174Asn	missense	Exon 5 of 7	ENSP00000412024.2	O95847-2
	SLC25A27	ENST00000603486.5	TSL:5	c.310C>A	p.His104Asn	missense	Exon 3 of 4	ENSP00000474781.1	Q5VTS8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1447212 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 720552

African (AFR) AF: 0.00 AC: 0 AN: 32962

American (AMR) AF: 0.00 AC: 0 AN: 43420

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25830

East Asian (EAS) AF: 0.00 AC: 0 AN: 39268

South Asian (SAS) AF: 0.00 AC: 0 AN: 84496

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53202

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 9.07e-7 AC: 1 AN: 1102500

Other (OTH) AF: 0.00 AC: 0 AN: 59812

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	0.011	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	21
DANN	Benign	0.94
DEOGEN2	Benign	0.076	T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.4	L
PhyloP100		4.1
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.23
Sift	Benign	0.30	T
Sift4G	Benign	0.27	T
Polyphen		0.12	B
Vest4		0.63
MutPred		0.38		Gain of catalytic residue at H174 (P = 0.0319)
MVP		0.66
MPC		0.67
ClinPred		0.81	D
GERP RS		5.1
PromoterAI		-0.037	Neutral
Varity_R		0.21
gMVP		0.82
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.26		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.26		Position offset: -13

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs201819031; hg19: chr6-46632524;