chr3-132576970-C-G

Variant summary

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

The NM_032169.5(ACAD11):​c.1820G>C​(p.Arg607Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,458,402 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. R607Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

ACAD11
NM_032169.5 missense

Scores

12
4
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.95
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]
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]

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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, 0.961

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ACAD11NM_032169.5 linkc.1820G>C p.Arg607Pro missense_variant Exon 16 of 20 ENST00000264990.11 NP_115545.3 Q709F0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ACAD11ENST00000264990.11 linkc.1820G>C p.Arg607Pro missense_variant Exon 16 of 20 1 NM_032169.5 ENSP00000264990.6 Q709F0-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1458402
Hom.:
0
Cov.:
28
AF XY:
0.00000138
AC XY:
1
AN XY:
725580
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.70
BayesDel_addAF
Pathogenic
0.53
D
BayesDel_noAF
Pathogenic
0.52
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.28
T
Eigen
Pathogenic
0.99
Eigen_PC
Pathogenic
0.88
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Pathogenic
0.98
D
M_CAP
Pathogenic
0.62
D
MetaRNN
Pathogenic
0.96
D
MetaSVM
Pathogenic
0.98
D
MutationAssessor
Pathogenic
3.6
H
PROVEAN
Pathogenic
-5.6
D
REVEL
Pathogenic
0.92
Sift
Uncertain
0.0070
D
Sift4G
Uncertain
0.014
D
Polyphen
1.0
D
Vest4
0.75
MutPred
0.88
Loss of catalytic residue at R607 (P = 0.0772);
MVP
0.99
MPC
0.76
ClinPred
1.0
D
GERP RS
5.5
Varity_R
0.61
gMVP
0.97

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.

Other links and lift over

hg19: chr3-132295814; API