NM_025247.6:c.82C>T

Variant names:

• chr12-111692791-C-T
• rs374462831
• NM_025247.6:c.82C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_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. 16/22 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.394
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09642556).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025247.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACAD10	NM_025247.6	MANE Select	c.82C>T	p.His28Tyr	missense	Exon 2 of 21	NP_079523.3
	ACAD10	NM_001136538.2		c.82C>T	p.His28Tyr	missense	Exon 2 of 22	NP_001130010.1	Q6JQN1-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACAD10	ENST00000313698.9	TSL:1 MANE Select	c.82C>T	p.His28Tyr	missense	Exon 2 of 21	ENSP00000325137.5	Q6JQN1-1
	ACAD10	ENST00000455480.6	TSL:1	c.82C>T	p.His28Tyr	missense	Exon 2 of 22	ENSP00000389813.2	Q6JQN1-5
	ACAD10	ENST00000507135.5	TSL:1	n.254C>T		non_coding_transcript_exon	Exon 2 of 7

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152160 Hom.: 0 Cov.: 32

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

GnomAD2 exomes AF: 0.0000915 AC: 23 AN: 251420 AF XY: 0.0000957

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 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.: 0 Cov.: 30 AF XY: 0.000267 AC XY: 194 AN XY: 727240

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000335 AC: 373 AN: 1112010

Other (OTH) AF: 0.0000994 AC: 6 AN: 60392

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152160 Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8 AN XY: 74332

African (AFR) AF: 0.000121 AC: 5 AN: 41432

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000213 Hom.: 0

Bravo AF: 0.000113

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000107 AC: 13

EpiCase AF: 0.000218

EpiControl AF: 0.000296

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	8.6
DANN	Benign	0.95
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.096	T
MetaSVM	Uncertain	0.033	D
MutationAssessor	Benign	0.69	N
PhyloP100		0.39
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.14
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.10	T
Polyphen		0.11	B
Vest4		0.24
MVP		0.86
MPC		0.48
ClinPred		0.046	T
GERP RS		1.8
Varity_R		0.061
gMVP		0.29
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs374462831; hg19: chr12-112130595;