12-111705876-T-G

Position:

• chr12-111705876-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_025247.6(ACAD10):​c.475T>G​(p.Phe159Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ACAD10 NM_025247.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.16

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACAD10	NM_025247.6	c.475T>G	p.Phe159Val	missense_variant	4/21	ENST00000313698.9	NP_079523.3
ACAD10	NM_001136538.2	c.475T>G	p.Phe159Val	missense_variant	4/22		NP_001130010.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACAD10	ENST00000313698.9	c.475T>G	p.Phe159Val	missense_variant	4/21	1	NM_025247.6	ENSP00000325137.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 04, 2024

The c.475T>G (p.F159V) alteration is located in exon 4 (coding exon 3) of the ACAD10 gene. This alteration results from a T to G substitution at nucleotide position 475, causing the phenylalanine (F) at amino acid position 159 to be replaced by a valine (V). 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	Uncertain	0.51
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	.;.;T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.76	T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.73	D;D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.1	.;L;L
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-4.8	D;D;D
REVEL	Uncertain	0.44
Sift	Uncertain	0.0090	D;D;D
Sift4G	Uncertain	0.0070	D;D;D
Polyphen		1.0	.;.;D
Vest4		0.67
MutPred		0.64		Gain of catalytic residue at S156 (P = 0);Gain of catalytic residue at S156 (P = 0);Gain of catalytic residue at S156 (P = 0);
MVP		0.43
MPC		0.68
ClinPred		0.98	D
GERP RS		6.0
Varity_R		0.55
gMVP		0.44

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-112143680;