3-132559074-G-A

Position:

• chr3-132559074-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032169.5(ACAD11):​c.2240C>T​(p.Thr747Ile) 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. 15/20 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)
• Consequence: ACAD11 NM_032169.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.162

Genes affected

ACAD11 (HGNC:30211): (acyl-CoA dehydrogenase family member 11) This gene encodes an acyl-CoA dehydrogenase enzyme with a preference for carbon chain lengths between 20 and 26. Naturally occurring read-through transcription occurs between the upstream gene NPHP3 (nephronophthisis 3 (adolescent)) and this gene. [provided by RefSeq, Aug 2015]

NPHP3-ACAD11 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38114476).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACAD11	NM_032169.5	c.2240C>T	p.Thr747Ile	missense_variant	20/20	ENST00000264990.11	NP_115545.3
NPHP3-ACAD11	NR_037804.1	n.6852C>T		non_coding_transcript_exon_variant	45/45

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACAD11	ENST00000264990.11	c.2240C>T	p.Thr747Ile	missense_variant	20/20	1	NM_032169.5	ENSP00000264990	P1
ACAD11	ENST00000485198.5	c.*721C>T		3_prime_UTR_variant, NMD_transcript_variant	18/18	1		ENSP00000419973
ACAD11	ENST00000469042.5	n.3026C>T		non_coding_transcript_exon_variant	18/18	2
ACAD11	ENST00000496418.5	n.2748C>T		non_coding_transcript_exon_variant	19/19	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Apr 08, 2024

The c.2240C>T (p.T747I) alteration is located in exon 20 (coding exon 20) of the ACAD11 gene. This alteration results from a C to T substitution at nucleotide position 2240, causing the threonine (T) at amino acid position 747 to be replaced by an isoleucine (I). 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	0.097
BayesDel_addAF	Benign	-0.0078	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	0.25
DANN	Benign	0.90
DEOGEN2	Benign	0.31	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.037	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	-0.51	N
MutationTaster	Benign	1.0	N;N;N
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.28
Sift	Benign	0.17	T
Sift4G	Benign	0.15	T
Polyphen		0.0010	B
Vest4		0.11
MutPred		0.56		Gain of glycosylation at Y744 (P = 0.0568);
MVP		0.76
MPC		0.16
ClinPred		0.050	T
GERP RS		0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
Varity_R		0.10
gMVP		0.47

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-132277918;