Variant 12-111692791-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_025247.6(ACAD10):c.82C>T(p.His28Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000248 in 1,614,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00026 ( 0 hom. )

Consequence

ACAD10
NM_025247.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.394

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09642556).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACAD10	NM_025247.6 link	c.82C>T	p.His28Tyr	missense_variant	Exon 2 of 21	ENST00000313698.9	NP_079523.3	Q6JQN1-1
ACAD10	NM_001136538.2 link	c.82C>T	p.His28Tyr	missense_variant	Exon 2 of 22		NP_001130010.1	Q6JQN1-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACAD10	ENST00000313698.9 link	c.82C>T	p.His28Tyr	missense_variant	Exon 2 of 21	1	NM_025247.6	ENSP00000325137.5		Q6JQN1-1

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000915

AC:

AN:

251420

Hom.:

AF XY:

0.0000957

AC XY:

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000193

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000261

AC:

382

AN:

1461882

Hom.:

Cov.:

AF XY:

0.000267

AC XY:

194

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000335

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.000118

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000213

Hom.:

Bravo

AF:

0.000113

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000107

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000296

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 01, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.82C>T (p.H28Y) alteration is located in exon 2 (coding exon 1) of the ACAD10 gene. This alteration results from a C to T substitution at nucleotide position 82, causing the histidine (H) at amino acid position 28 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.26

CADD

Benign

8.6

DANN

Benign

0.95

DEOGEN2

Benign

0.024

T;.;.;T

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.40

T;T;T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.096

T;T;T;T

MetaSVM

Uncertain

0.033

MutationAssessor

Benign

0.69

.;.;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.5

N;N;N;N

REVEL

Benign

0.14

Sift

Uncertain

0.0090

D;D;D;D

Sift4G

Benign

0.10

T;D;D;D

Polyphen

0.11

.;.;.;B

Vest4

0.24, 0.23, 0.21

MVP

0.86

MPC

0.48

ClinPred

0.046

GERP RS

1.8

Varity_R

0.061

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over