Genetic Variant SLC25A42:c.*385C>T (chr19-19111261-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_178526.5(SLC25A42):c.*385C>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 0.786 in 242,172 control chromosomes in the GnomAD database, including 75,582 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 0.77 ( 45642 hom., cov: 33)

Exomes 𝑓: 0.81 ( 29940 hom. )

Consequence

SLC25A42
NM_178526.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.808

Publications

11 publications found

Variant links:

Genes affected

SLC25A42 (HGNC:28380): (solute carrier family 25 member 42) This gene encodes a solute carrier family 25 protein. Solute carrier family 25 proteins are localized to mitochondria and play critical roles in the transport of molecules across the inner mitochondrial membrane. The encoded protein is a mitochondrial transporter for coenzyme A (CoA) and adenosine 3',5'-diphosphate. [provided by RefSeq, Feb 2012]

SLC25A42 Gene-Disease associations (from GenCC):

metabolic crises, recurrent, with variable encephalomyopathic features and neurologic regression
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

SLC25A42 links:

Genome browser will be placed here

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=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A42	NM_178526.5 link	c.*385C>T		3_prime_UTR_variant	Exon 8 of 8	ENST00000318596.8	NP_848621.2	Q86VD7A0A024R7K2Q8NHH2
SLC25A42	NM_001321544.2 link	c.*385C>T		3_prime_UTR_variant	Exon 8 of 8		NP_001308473.1	Q86VD7A0A024R7K2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A42	ENST00000318596.8 link	c.*385C>T		3_prime_UTR_variant	Exon 8 of 8	1	NM_178526.5	ENSP00000326693.6		Q86VD7

Frequencies

GnomAD3 genomes

AF:

0.770

AC:

117042

AN:

152046

Hom.:

45624

Cov.:

show subpopulations

Gnomad AFR

AF:

0.643

Gnomad AMI

AF:

0.935

Gnomad AMR

AF:

0.818

Gnomad ASJ

AF:

0.828

Gnomad EAS

AF:

0.906

Gnomad SAS

AF:

0.810

Gnomad FIN

AF:

0.765

Gnomad MID

AF:

0.782

Gnomad NFE

AF:

0.817

Gnomad OTH

AF:

0.801

GnomAD4 exome

AF:

0.813

AC:

73184

AN:

90008

Hom.:

29940

Cov.:

AF XY:

0.814

AC XY:

39096

AN XY:

48028

show subpopulations

African (AFR)

AF:

0.641

AC:

915

AN:

1428

American (AMR)

AF:

0.835

AC:

3380

AN:

4050

Ashkenazi Jewish (ASJ)

AF:

0.842

AC:

1907

AN:

2266

East Asian (EAS)

AF:

0.910

AC:

2164

AN:

2378

South Asian (SAS)

AF:

0.809

AC:

11685

AN:

14450

European-Finnish (FIN)

AF:

0.777

AC:

3421

AN:

4404

Middle Eastern (MID)

AF:

0.779

AC:

304

AN:

390

European-Non Finnish (NFE)

AF:

0.815

AC:

45392

AN:

55692

Other (OTH)

AF:

0.811

AC:

4016

AN:

4950

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

655

1310

1964

2619

3274

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

264

528

792

1056

1320

<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:

0.770

AC:

117103

AN:

152164

Hom.:

45642

Cov.:

AF XY:

0.770

AC XY:

57274

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.643

AC:

26693

AN:

41508

American (AMR)

AF:

0.818

AC:

12505

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.828

AC:

2872

AN:

3468

East Asian (EAS)

AF:

0.907

AC:

4683

AN:

5166

South Asian (SAS)

AF:

0.811

AC:

3920

AN:

4832

European-Finnish (FIN)

AF:

0.765

AC:

8107

AN:

10596

Middle Eastern (MID)

AF:

0.769

AC:

226

AN:

294

European-Non Finnish (NFE)

AF:

0.817

AC:

55554

AN:

67982

Other (OTH)

AF:

0.799

AC:

1690

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1378

2756

4134

5512

6890

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

858

1716

2574

3432

4290

<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:

0.801

Hom.:

21780

Bravo

AF:

0.772

Asia WGS

AF:

0.831

AC:

2894

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.16

(source)

DANN

Benign

0.77

PhyloP100

-0.81

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