chr3-132579514-T-C

Variant names:

• chr3-132579514-T-C
• NM_032169.5:c.1666A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_032169.5(ACAD11):​c.1666A>G​(p.Thr556Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 3.76
• Publications: 0 publications found

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:48351): (NPHP3-ACAD11 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring NPHP3 (nephronophthisis 3, adolescent) and ACAD11 (acyl-CoA dehydrogenase family, member 11) genes on chromosome 3. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032169.5. 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
	ACAD11	NM_032169.5	MANE Select	c.1666A>G	p.Thr556Ala	missense	Exon 14 of 20	NP_115545.3
	NPHP3-ACAD11	NR_037804.1		n.5668A>G		non_coding_transcript_exon	Exon 40 of 45
	ACAD11	NR_132426.2		n.1724A>G		non_coding_transcript_exon	Exon 14 of 19

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACAD11	ENST00000264990.11	TSL:1 MANE Select	c.1666A>G	p.Thr556Ala	missense	Exon 14 of 20	ENSP00000264990.6	Q709F0-1
	ACAD11	ENST00000485198.5	TSL:1	n.*147A>G		non_coding_transcript_exon	Exon 12 of 18	ENSP00000419973.1	F8WEV0
	ACAD11	ENST00000485198.5	TSL:1	n.*147A>G		3_prime_UTR	Exon 12 of 18	ENSP00000419973.1	F8WEV0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

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	0.11
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.67	D
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.60	T
M_CAP	Uncertain	0.23	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Uncertain	0.79	D
MutationAssessor	Pathogenic	3.2	M
PhyloP100		3.8
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.60
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.034	B
Vest4		0.13
MutPred		0.81		Gain of MoRF binding (P = 0.0977)
MVP		0.94
MPC		0.18
ClinPred		0.94	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.23
gMVP		0.72
Mutation Taster		=76/24	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

hg19: chr3-132298358;