Genetic Variant ACAD10:c.187+8A>G (chr12-111692904-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_025247.6(ACAD10):c.187+8A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0397 in 1,612,982 control chromosomes in the GnomAD database, including 11,792 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.078 ( 1618 hom., cov: 32)

Exomes 𝑓: 0.036 ( 10174 hom. )

Consequence

ACAD10
NM_025247.6 splice_region, intron

Scores

Splicing: ADA: 0.00003145

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.350

Variant links:

Genes affected

ACAD10 (HGNC:21597): (acyl-CoA dehydrogenase family member 10) This gene encodes a member of the acyl-CoA dehydrogenase family of enzymes (ACADs), which participate in the beta-oxidation of fatty acids in mitochondria. The encoded enzyme contains a hydrolase domain at the N-terminal portion, a serine/threonine protein kinase catlytic domain in the central region, and a conserved ACAD domain at the C-terminus. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Nov 2008]

ACAD10 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=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACAD10	NM_025247.6 link	c.187+8A>G		splice_region_variant, intron_variant	Intron 2 of 20	ENST00000313698.9	NP_079523.3	Q6JQN1-1
ACAD10	NM_001136538.2 link	c.187+8A>G		splice_region_variant, intron_variant	Intron 2 of 21		NP_001130010.1	Q6JQN1-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACAD10	ENST00000313698.9 link	c.187+8A>G		splice_region_variant, intron_variant	Intron 2 of 20	1	NM_025247.6	ENSP00000325137.5		Q6JQN1-1

Frequencies

GnomAD3 genomes

AF:

0.0781

AC:

11870

AN:

151946

Hom.:

1620

Cov.:

show subpopulations

Gnomad AFR

AF:

0.143

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.116

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.621

Gnomad SAS

AF:

0.102

Gnomad FIN

AF:

0.00208

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.00357

Gnomad OTH

AF:

0.0824

GnomAD2 exomes

AF:

0.0971

AC:

24184

AN:

249034

AF XY:

0.0873

show subpopulations

Gnomad AFR exome

AF:

0.153

Gnomad AMR exome

AF:

0.185

Gnomad ASJ exome

AF:

0.00524

Gnomad EAS exome

AF:

0.654

Gnomad FIN exome

AF:

0.00368

Gnomad NFE exome

AF:

0.00395

Gnomad OTH exome

AF:

0.0560

GnomAD4 exome

AF:

0.0357

AC:

52181

AN:

1460918

Hom.:

10174

Cov.:

AF XY:

0.0358

AC XY:

26026

AN XY:

726750

show subpopulations

Gnomad4 AFR exome

AF:

0.148

AC:

4964

AN:

33462

Gnomad4 AMR exome

AF:

0.175

AC:

7816

AN:

44646

Gnomad4 ASJ exome

AF:

0.00526

AC:

137

AN:

26058

Gnomad4 EAS exome

AF:

0.645

AC:

25584

AN:

39682

Gnomad4 SAS exome

AF:

0.0798

AC:

6880

AN:

86178

Gnomad4 FIN exome

AF:

0.00334

AC:

178

AN:

53294

Gnomad4 NFE exome

AF:

0.00262

AC:

2914

AN:

1111486

Gnomad4 Remaining exome

AF:

0.0574

AC:

3464

AN:

60350

Heterozygous variant carriers

1733

3465

5198

6930

8663

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

684

1368

2052

2736

3420

<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:

0.0782

AC:

11892

AN:

152064

Hom.:

1618

Cov.:

AF XY:

0.0830

AC XY:

6170

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.143

AC:

0.143343

AN:

0.143343

Gnomad4 AMR

AF:

0.117

AC:

0.116915

AN:

0.116915

Gnomad4 ASJ

AF:

0.00548

AC:

0.00547866

AN:

0.00547866

Gnomad4 EAS

AF:

0.620

AC:

0.620482

AN:

0.620482

Gnomad4 SAS

AF:

0.102

AC:

0.102447

AN:

0.102447

Gnomad4 FIN

AF:

0.00208

AC:

0.00207822

AN:

0.00207822

Gnomad4 NFE

AF:

0.00357

AC:

0.00357469

AN:

0.00357469

Gnomad4 OTH

AF:

0.0820

AC:

0.0819905

AN:

0.0819905

Heterozygous variant carriers

425

850

1276

1701

2126

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

120

240

360

480

600

<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:

0.0293

Hom.:

216

Bravo

AF:

0.0950

Asia WGS

AF:

0.260

AC:

902

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

6.7

DANN

Benign

0.57

Mutation Taster

=100/0

polymorphism (auto)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000031

dbscSNV1_RF

Benign

0.0

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over