chr3-132559021-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_032169.5(ACAD11):​c.2293G>A​(p.Ala765Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000192 in 1,613,458 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 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

ACAD11
NM_032169.5 missense

Scores

8
7
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.90
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 Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.953

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ACAD11NM_032169.5 linkuse as main transcriptc.2293G>A p.Ala765Thr missense_variant 20/20 ENST00000264990.11
NPHP3-ACAD11NR_037804.1 linkuse as main transcriptn.6905G>A non_coding_transcript_exon_variant 45/45

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ACAD11ENST00000264990.11 linkuse as main transcriptc.2293G>A p.Ala765Thr missense_variant 20/201 NM_032169.5 P1Q709F0-1
ACAD11ENST00000485198.5 linkuse as main transcriptc.*774G>A 3_prime_UTR_variant, NMD_transcript_variant 18/181
ACAD11ENST00000469042.5 linkuse as main transcriptn.3079G>A non_coding_transcript_exon_variant 18/182
ACAD11ENST00000496418.5 linkuse as main transcriptn.2801G>A non_coding_transcript_exon_variant 19/192

Frequencies

GnomAD3 genomes
AF:
0.0000658
AC:
10
AN:
152032
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000217
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
250902
Hom.:
0
AF XY:
0.0000369
AC XY:
5
AN XY:
135620
show subpopulations
Gnomad AFR exome
AF:
0.000246
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000144
AC:
21
AN:
1461426
Hom.:
0
Cov.:
30
AF XY:
0.0000165
AC XY:
12
AN XY:
727016
show subpopulations
Gnomad4 AFR exome
AF:
0.000269
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000812
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000658
AC:
10
AN:
152032
Hom.:
0
Cov.:
32
AF XY:
0.000108
AC XY:
8
AN XY:
74258
show subpopulations
Gnomad4 AFR
AF:
0.000217
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000386
Hom.:
0
Bravo
AF:
0.0000718
ExAC
AF:
0.0000247
AC:
3

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 10, 2022The c.2293G>A (p.A765T) alteration is located in exon 20 (coding exon 20) of the ACAD11 gene. This alteration results from a G to A substitution at nucleotide position 2293, causing the alanine (A) at amino acid position 765 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
0.21
BayesDel_addAF
Pathogenic
0.28
D
BayesDel_noAF
Pathogenic
0.45
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.75
D
Eigen
Uncertain
0.67
Eigen_PC
Uncertain
0.48
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.99
D
M_CAP
Uncertain
0.25
D
MetaRNN
Pathogenic
0.95
D
MetaSVM
Pathogenic
1.1
D
MutationAssessor
Pathogenic
3.4
M
MutationTaster
Benign
1.0
D;D;D
PROVEAN
Uncertain
-3.0
D
REVEL
Pathogenic
0.79
Sift
Benign
0.040
D
Sift4G
Uncertain
0.018
D
Polyphen
1.0
D
Vest4
0.73
MVP
0.98
MPC
0.56
ClinPred
0.89
D
GERP RS
5.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.20
gMVP
0.76

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: rs778814949; hg19: chr3-132277865; COSMIC: COSV53898016; API