Genetic Variant ACAD11:p.Asp771His (chr3-132559003-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_032169.5(ACAD11):c.2311G>C(p.Asp771His) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,396 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D771N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ACAD11
NM_032169.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.17

Publications

0 publications found

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: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]

NPHP3-ACAD11 links:

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ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ACAD11	NM_032169.5	MANE Select	c.2311G>C	p.Asp771His	missense	Exon 20 of 20	NP_115545.3
NPHP3-ACAD11	NR_037804.1		n.6923G>C		non_coding_transcript_exon	Exon 45 of 45
ACAD11	NR_132426.2		n.2979G>C		non_coding_transcript_exon	Exon 19 of 19

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACAD11	ENST00000264990.11	TSL:1 MANE Select	c.2311G>C	p.Asp771His	missense	Exon 20 of 20	ENSP00000264990.6	Q709F0-1
ACAD11	ENST00000485198.5	TSL:1	n.*792G>C		non_coding_transcript_exon	Exon 18 of 18	ENSP00000419973.1	F8WEV0
ACAD11	ENST00000485198.5	TSL:1	n.*792G>C		3_prime_UTR	Exon 18 of 18	ENSP00000419973.1	F8WEV0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461396

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727016

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44670

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.00

AC:

AN:

86172

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53386

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111726

Other (OTH)

AF:

0.00

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.066

Eigen

Benign

0.063

Eigen_PC

Benign

-0.060

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.79

M_CAP

Uncertain

0.17

MetaRNN

Uncertain

0.53

MetaSVM

Uncertain

0.59

MutationAssessor

Uncertain

2.3

PhyloP100

4.2

PROVEAN

Benign

-1.6

REVEL

Uncertain

0.42

Sift

Benign

0.28

Sift4G

Benign

0.16

Polyphen

0.99

Vest4

0.37

MutPred

0.29

Gain of MoRF binding (P = 0.0504)

MVP

0.92

MPC

0.62

ClinPred

0.59

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.092

gMVP

0.68

Mutation Taster

=53/47

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over