3-132575837-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_032169.5(ACAD11):​c.1936G>A​(p.Ala646Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000211 in 1,614,016 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 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

ACAD11
NM_032169.5 missense

Scores

6
6
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.79
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.748

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ACAD11NM_032169.5 linkuse as main transcriptc.1936G>A p.Ala646Thr missense_variant 17/20 ENST00000264990.11
NPHP3-ACAD11NR_037804.1 linkuse as main transcriptn.6548G>A non_coding_transcript_exon_variant 42/45

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ACAD11ENST00000264990.11 linkuse as main transcriptc.1936G>A p.Ala646Thr missense_variant 17/201 NM_032169.5 P1Q709F0-1
ACAD11ENST00000485198.5 linkuse as main transcriptc.*417G>A 3_prime_UTR_variant, NMD_transcript_variant 15/181
ACAD11ENST00000496418.5 linkuse as main transcriptn.2444G>A non_coding_transcript_exon_variant 16/192
ACAD11ENST00000469042.5 linkuse as main transcriptn.2787+1107G>A intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152078
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:
0.00
Gnomad SAS
AF:
0.000208
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251046
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135644
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000545
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000265
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000226
AC:
33
AN:
1461820
Hom.:
0
Cov.:
31
AF XY:
0.0000234
AC XY:
17
AN XY:
727208
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000243
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152196
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74420
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189
ExAC
AF:
0.00000824
AC:
1
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 GeneticsMar 20, 2024The c.1936G>A (p.A646T) alteration is located in exon 17 (coding exon 17) of the ACAD11 gene. This alteration results from a G to A substitution at nucleotide position 1936, causing the alanine (A) at amino acid position 646 to be replaced by a threonine (T). 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
0.092
BayesDel_addAF
Pathogenic
0.20
D
BayesDel_noAF
Pathogenic
0.21
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.59
D
Eigen
Benign
0.15
Eigen_PC
Benign
0.16
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.89
D
M_CAP
Uncertain
0.12
D
MetaRNN
Pathogenic
0.75
D
MetaSVM
Pathogenic
0.94
D
MutationAssessor
Pathogenic
3.1
M
MutationTaster
Benign
1.0
D;D;D
PROVEAN
Benign
-2.1
N
REVEL
Pathogenic
0.71
Sift
Benign
0.068
T
Sift4G
Uncertain
0.060
T
Polyphen
0.33
B
Vest4
0.52
MutPred
0.81
Loss of MoRF binding (P = 0.1289);
MVP
0.96
MPC
0.17
ClinPred
0.46
T
GERP RS
4.7
Varity_R
0.099
gMVP
0.81

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: rs766955027; hg19: chr3-132294681; COSMIC: COSV53900897; COSMIC: COSV53900897; API