chr3-132561166-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_032169.5(ACAD11):​c.2053C>T​(p.Arg685Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000161 in 1,613,518 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

ACAD11
NM_032169.5 missense

Scores

14
2
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.88
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.917

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ACAD11NM_032169.5 linkuse as main transcriptc.2053C>T p.Arg685Cys missense_variant 18/20 ENST00000264990.11
NPHP3-ACAD11NR_037804.1 linkuse as main transcriptn.6665C>T non_coding_transcript_exon_variant 43/45

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ACAD11ENST00000264990.11 linkuse as main transcriptc.2053C>T p.Arg685Cys missense_variant 18/201 NM_032169.5 P1Q709F0-1
ACAD11ENST00000485198.5 linkuse as main transcriptc.*534C>T 3_prime_UTR_variant, NMD_transcript_variant 16/181
ACAD11ENST00000469042.5 linkuse as main transcriptn.2839C>T non_coding_transcript_exon_variant 16/182
ACAD11ENST00000496418.5 linkuse as main transcriptn.2561C>T non_coding_transcript_exon_variant 17/192

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152012
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000385
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
250986
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135626
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000882
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000157
AC:
23
AN:
1461388
Hom.:
0
Cov.:
30
AF XY:
0.0000206
AC XY:
15
AN XY:
726994
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000117
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152130
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000540
Hom.:
0
Bravo
AF:
0.0000529
ExAC
AF:
0.0000494
AC:
6

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 submitterclinical testingAmbry GeneticsNov 18, 2022The c.2053C>T (p.R685C) alteration is located in exon 18 (coding exon 18) of the ACAD11 gene. This alteration results from a C to T substitution at nucleotide position 2053, causing the arginine (R) at amino acid position 685 to be replaced by a cysteine (C). 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
0.25
BayesDel_addAF
Pathogenic
0.39
D
BayesDel_noAF
Pathogenic
0.55
CADD
Pathogenic
33
DANN
Pathogenic
1.0
DEOGEN2
Pathogenic
0.84
D
Eigen
Pathogenic
0.89
Eigen_PC
Pathogenic
0.76
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.95
D
M_CAP
Pathogenic
0.44
D
MetaRNN
Pathogenic
0.92
D
MetaSVM
Pathogenic
1.0
D
MutationAssessor
Pathogenic
4.5
H
MutationTaster
Benign
1.0
D;D;D
PROVEAN
Pathogenic
-7.5
D
REVEL
Pathogenic
0.90
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.97
MutPred
0.75
Loss of MoRF binding (P = 0.003);
MVP
0.99
MPC
0.76
ClinPred
1.0
D
GERP RS
3.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.15
gMVP
0.86

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs578141275; hg19: chr3-132280010; API