Variant 3-132561139-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.79

Variant links:

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]

ACAD11 links:

NPHP3-ACAD11 (HGNC:):

NPHP3-ACAD11 links:

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ACMG classification

Classification made for transcript

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/exons	MANE	UniProt
ACAD11	NM_032169.5 linkuse as main transcript	c.2080A>G	p.Ser694Gly	missense_variant	18/20	ENST00000264990.11
NPHP3-ACAD11	NR_037804.1 linkuse as main transcript	n.6692A>G		non_coding_transcript_exon_variant	43/45

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACAD11	ENST00000264990.11 linkuse as main transcript	c.2080A>G	p.Ser694Gly	missense_variant	18/20	1	NM_032169.5	P1	Q709F0-1
ACAD11	ENST00000485198.5 linkuse as main transcript	c.*561A>G		3_prime_UTR_variant, NMD_transcript_variant	16/18	1
ACAD11	ENST00000469042.5 linkuse as main transcript	n.2866A>G		non_coding_transcript_exon_variant	16/18	2
ACAD11	ENST00000496418.5 linkuse as main transcript	n.2588A>G		non_coding_transcript_exon_variant	17/19	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461384

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726992

show subpopulations

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.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 05, 2023

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

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.45

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.0042

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.083

MetaRNN

Benign

0.28

MetaSVM

Uncertain

0.027

MutationAssessor

Benign

1.7

MutationTaster

Benign

0.91

N;N;N

PROVEAN

Benign

-1.9

REVEL

Uncertain

0.32

Sift

Benign

0.38

Sift4G

Benign

0.37

Polyphen

0.47

Vest4

0.30

MutPred

0.43

Gain of glycosylation at S694 (P = 0.1015);

MVP

0.91

MPC

0.20

ClinPred

0.39

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over