12-111702245-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025247.6(ACAD10):c.271T>C(p.Phe91Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ACAD10 NM_025247.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.83

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

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=0.14557403).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACAD10	NM_025247.6	c.271T>C	p.Phe91Leu	missense_variant	3/21	ENST00000313698.9
ACAD10	NM_001136538.2	c.271T>C	p.Phe91Leu	missense_variant	3/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACAD10	ENST00000313698.9	c.271T>C	p.Phe91Leu	missense_variant	3/21	1	NM_025247.6	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1454588 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724086

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Oct 20, 2023

The c.271T>C (p.F91L) alteration is located in exon 3 (coding exon 2) of the ACAD10 gene. This alteration results from a T to C substitution at nucleotide position 271, causing the phenylalanine (F) at amino acid position 91 to be replaced by a leucine (L). 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	Pathogenic	0.79
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
Cadd	Benign	18
Dann	Uncertain	0.97
DEOGEN2	Benign	0.031	T;.;.;T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.030
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.65	T;T;T;T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.15	T;T;T;T
MetaSVM	Benign	-0.82	T
MutationTaster	Benign	0.92	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-2.4	N;N;N;N
REVEL	Benign	0.030
Sift	Benign	0.31	T;T;T;T
Sift4G	Benign	0.23	T;T;T;T
Polyphen		0.011	.;.;.;B
Vest4		0.29, 0.36, 0.41
MutPred		0.47		Gain of catalytic residue at M89 (P = 0.0075);Gain of catalytic residue at M89 (P = 0.0075);Gain of catalytic residue at M89 (P = 0.0075);Gain of catalytic residue at M89 (P = 0.0075);
MVP		0.22
MPC		0.16
ClinPred		0.41	T
GERP RS		4.5
Varity_R		0.078
gMVP		0.57

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: chr12-112140049;