3-132561139-T-C

Variant names:

• chr3-132561139-T-C
• NM_032169.5:c.2080A>G

Variant summary

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

The NM_032169.5(ACAD11):​c.2080A>G​(p.Ser694Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,384 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ACAD11 NM_032169.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.79

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

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=0.27735117).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACAD11	NM_032169.5	c.2080A>G	p.Ser694Gly	missense_variant	Exon 18 of 20	ENST00000264990.11	NP_115545.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACAD11	ENST00000264990.11	c.2080A>G	p.Ser694Gly	missense_variant	Exon 18 of 20	1	NM_032169.5	ENSP00000264990.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461384 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726992

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: 9.00e-7

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

Apr 05, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2080A>G (p.S694G) alteration is located in exon 18 (coding exon 18) of the ACAD11 gene. This alteration results from a A to G substitution at nucleotide position 2080, causing the serine (S) at amino acid position 694 to be replaced by a glycine (G). 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	0.089
BayesDel_addAF	Uncertain	0.062	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.45	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.0042
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.083	D
MetaRNN	Benign	0.28	T
MetaSVM	Uncertain	0.027	D
MutationAssessor	Benign	1.7	L
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.32
Sift	Benign	0.38	T
Sift4G	Benign	0.37	T
Polyphen		0.47	P
Vest4		0.30
MutPred		0.43		Gain of glycosylation at S694 (P = 0.1015);
MVP		0.91
MPC		0.20
ClinPred		0.39	T
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.36

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: chr3-132279983;