Genetic Variant NM_004277.5:c.*684C>T (chr6-46677138-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.03

Publications

42 publications found

Variant links:

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]

SLC25A27 links:

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

TDRD6-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SLC25A27	NM_004277.5 link	c.*684C>T		3_prime_UTR_variant	Exon 9 of 9	ENST00000371347.10	NP_004268.3	O95847-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A27	ENST00000371347.10 link	c.*684C>T		3_prime_UTR_variant	Exon 9 of 9	1	NM_004277.5	ENSP00000360398.3		O95847-1

Frequencies

GnomAD3 genomes

AF:

0.293

AC:

44481

AN:

151888

Hom.:

6693

Cov.:

show subpopulations

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.:

AF XY:

0.347

AC XY:

1872

AN XY:

5394

show subpopulations

African (AFR)

AF:

0.326

AC:

AN:

172

American (AMR)

AF:

0.379

AC:

392

AN:

1034

Ashkenazi Jewish (ASJ)

AF:

0.358

AC:

AN:

232

East Asian (EAS)

AF:

0.192

AC:

AN:

442

South Asian (SAS)

AF:

0.582

AC:

463

AN:

796

European-Finnish (FIN)

AF:

0.326

AC:

144

AN:

442

Middle Eastern (MID)

AF:

0.360

AC:

AN:

European-Non Finnish (NFE)

AF:

0.319

AC:

2111

AN:

6612

Other (OTH)

AF:

0.338

AC:

208

AN:

616

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

116

232

349

465

581

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.293

AC:

44511

AN:

152006

Hom.:

6691

Cov.:

AF XY:

0.296

AC XY:

22009

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.268

AC:

11091

AN:

41448

American (AMR)

AF:

0.353

AC:

5384

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.341

AC:

1184

AN:

3468

East Asian (EAS)

AF:

0.206

AC:

1066

AN:

5166

South Asian (SAS)

AF:

0.521

AC:

2509

AN:

4818

European-Finnish (FIN)

AF:

0.300

AC:

3170

AN:

10566

Middle Eastern (MID)

AF:

0.337

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.281

AC:

19078

AN:

67962

Other (OTH)

AF:

0.317

AC:

668

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1600

3200

4799

6399

7999

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

468

936

1404

1872

2340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.289

Hom.:

29083

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

(source)

DANN

Benign

0.67

PhyloP100

-1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over