11-77869729-C-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_024684.4(AAMDC):c.140C>T(p.Pro47Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,613,730 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 0.000013 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
AAMDC
NM_024684.4 missense
NM_024684.4 missense
Scores
9
7
3
Clinical Significance
Conservation
PhyloP100: 6.83
Genes affected
AAMDC (HGNC:30205): (adipogenesis associated Mth938 domain containing) Predicted to be involved in positive regulation of fat cell differentiation. Predicted to act upstream of or within negative regulation of apoptotic process and positive regulation of transcription by RNA polymerase II. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]
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, 0.779
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AAMDC | NM_024684.4 | c.140C>T | p.Pro47Leu | missense_variant | 3/4 | ENST00000393427.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AAMDC | ENST00000393427.7 | c.140C>T | p.Pro47Leu | missense_variant | 3/4 | 1 | NM_024684.4 | P1 | |
ENST00000530972.1 | n.363G>A | non_coding_transcript_exon_variant | 1/2 | 2 | |||||
ENST00000525594.1 | n.111+2423G>A | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152192Hom.: 0 Cov.: 31
GnomAD3 genomes
AF:
AC:
2
AN:
152192
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251386Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135858
GnomAD3 exomes
AF:
AC:
7
AN:
251386
Hom.:
AF XY:
AC XY:
3
AN XY:
135858
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461538Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 727086
GnomAD4 exome
AF:
AC:
7
AN:
1461538
Hom.:
Cov.:
30
AF XY:
AC XY:
2
AN XY:
727086
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152192Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74342
GnomAD4 genome
AF:
AC:
2
AN:
152192
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
74342
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ExAC
AF:
AC:
2
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 submitter | clinical testing | Ambry Genetics | Apr 19, 2024 | The c.140C>T (p.P47L) alteration is located in exon 3 (coding exon 2) of the AAMDC gene. This alteration results from a C to T substitution at nucleotide position 140, causing the proline (P) at amino acid position 47 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
.;T;T;.;.;.;D;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;.;D;D;.;D;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;M;M;.;.;.;.;.
MutationTaster
Benign
D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D;D;.;D;D
REVEL
Pathogenic
Sift
Uncertain
D;T;T;D;D;.;D;T
Sift4G
Pathogenic
D;D;D;D;D;D;D;D
Polyphen
D;D;D;D;.;.;.;.
Vest4
MutPred
Gain of catalytic residue at P47 (P = 0.0017);Gain of catalytic residue at P47 (P = 0.0017);Gain of catalytic residue at P47 (P = 0.0017);Gain of catalytic residue at P47 (P = 0.0017);Gain of catalytic residue at P47 (P = 0.0017);Gain of catalytic residue at P47 (P = 0.0017);.;.;
MVP
MPC
0.15
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 11
Find out detailed SpliceAI scores and Pangolin per-transcript scores at