Genetic Variant NM_001282195.2:c.719+110T>A (chrX-130364862-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001282195.2(SLC25A14):c.719+110T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 1,115,878 control chromosomes in the GnomAD database, including 73,788 homozygotes. There are 149,417 hemizygotes in GnomAD. 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 0.41 ( 6769 hom., 12880 hem., cov: 22)

Exomes 𝑓: 0.44 ( 67019 hom. 136537 hem. )

Consequence

SLC25A14
NM_001282195.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.632

Publications

4 publications found

Variant links:

Genes affected

SLC25A14 (HGNC:10984): (solute carrier family 25 member 14) Mitochondrial uncoupling proteins (UCP) are members of the larger family of mitochondrial anion carrier proteins (MACP). Uncoupling proteins separate oxidative phosphorylation from ATP synthesis with energy dissipated as heat, also referred to as the mitochondrial proton leak. Uncoupling proteins 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. This gene is widely expressed in many tissues with the greatest abundance in brain and testis. Alternative splicing results in multiple transcript variants. A pseudogene of this gene has been defined on chromosome 4. [provided by RefSeq, Aug 2013]

SLC25A14 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=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A14	NM_001282195.2 link	c.719+110T>A		intron_variant	Intron 8 of 10	ENST00000545805.6	NP_001269124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A14	ENST00000545805.6 link	c.719+110T>A		intron_variant	Intron 8 of 10	5	NM_001282195.2	ENSP00000444642.2		O95258-1

Frequencies

GnomAD3 genomes

AF:

0.410

AC:

45286

AN:

110588

Hom.:

6773

Cov.:

show subpopulations

Gnomad AFR

AF:

0.387

Gnomad AMI

AF:

0.344

Gnomad AMR

AF:

0.372

Gnomad ASJ

AF:

0.407

Gnomad EAS

AF:

0.374

Gnomad SAS

AF:

0.407

Gnomad FIN

AF:

0.321

Gnomad MID

AF:

0.426

Gnomad NFE

AF:

0.443

Gnomad OTH

AF:

0.400

GnomAD4 exome

AF:

0.439

AC:

441241

AN:

1005236

Hom.:

67019

Cov.:

AF XY:

0.445

AC XY:

136537

AN XY:

306706

show subpopulations

African (AFR)

AF:

0.391

AC:

9314

AN:

23796

American (AMR)

AF:

0.378

AC:

10106

AN:

26758

Ashkenazi Jewish (ASJ)

AF:

0.429

AC:

7212

AN:

16818

East Asian (EAS)

AF:

0.361

AC:

9053

AN:

25109

South Asian (SAS)

AF:

0.421

AC:

20682

AN:

49076

European-Finnish (FIN)

AF:

0.369

AC:

10424

AN:

28269

Middle Eastern (MID)

AF:

0.364

AC:

1351

AN:

3716

European-Non Finnish (NFE)

AF:

0.450

AC:

355518

AN:

790355

Other (OTH)

AF:

0.425

AC:

17581

AN:

41339

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

7485

14970

22455

29940

37425

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12268

24536

36804

49072

61340

<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:

0.409

AC:

45274

AN:

110642

Hom.:

6769

Cov.:

AF XY:

0.391

AC XY:

12880

AN XY:

32920

show subpopulations

African (AFR)

AF:

0.387

AC:

11760

AN:

30414

American (AMR)

AF:

0.371

AC:

3873

AN:

10434

Ashkenazi Jewish (ASJ)

AF:

0.407

AC:

1074

AN:

2636

East Asian (EAS)

AF:

0.374

AC:

1316

AN:

3515

South Asian (SAS)

AF:

0.406

AC:

1068

AN:

2628

European-Finnish (FIN)

AF:

0.321

AC:

1874

AN:

5838

Middle Eastern (MID)

AF:

0.433

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.443

AC:

23390

AN:

52779

Other (OTH)

AF:

0.394

AC:

593

AN:

1505

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

990

1979

2969

3958

4948

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

450

900

1350

1800

2250

<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:

0.424

Hom.:

2876

Bravo

AF:

0.414

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.62

(source)

DANN

Benign

0.58

PhyloP100

-0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

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