19-10581591-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_005498.5(AP1M2):c.442C>T(p.Arg148Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000137 in 1,461,576 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: not found (cov: 31)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
AP1M2
NM_005498.5 missense
NM_005498.5 missense
Scores
4
11
4
Clinical Significance
Conservation
PhyloP100: 6.15
Genes affected
AP1M2 (HGNC:558): (adaptor related protein complex 1 subunit mu 2) This gene encodes a subunit of the heterotetrameric adaptor-related protein comlex 1 (AP-1), which belongs to the adaptor complexes medium subunits family. This protein is capable of interacting with tyrosine-based sorting signals. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]
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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, 0.762
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AP1M2 | NM_005498.5 | c.442C>T | p.Arg148Trp | missense_variant | 5/12 | ENST00000250244.11 | NP_005489.2 | |
AP1M2 | NM_001300887.2 | c.442C>T | p.Arg148Trp | missense_variant | 5/12 | NP_001287816.1 | ||
AP1M2 | XM_047438018.1 | c.364C>T | p.Arg122Trp | missense_variant | 5/12 | XP_047293974.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AP1M2 | ENST00000250244.11 | c.442C>T | p.Arg148Trp | missense_variant | 5/12 | 1 | NM_005498.5 | ENSP00000250244.5 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249114Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135080
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GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461576Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 727054
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GnomAD4 genome Cov.: 31
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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 | Jan 17, 2024 | The c.442C>T (p.R148W) alteration is located in exon 5 (coding exon 5) of the AP1M2 gene. This alteration results from a C to T substitution at nucleotide position 442, causing the arginine (R) at amino acid position 148 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
.;T;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
M;M;.;.;.
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
.;D;.;.;.
REVEL
Uncertain
Sift
Pathogenic
.;D;.;.;.
Sift4G
Uncertain
D;D;.;.;D
Polyphen
D;D;.;.;.
Vest4
MutPred
Loss of disorder (P = 0.012);Loss of disorder (P = 0.012);.;.;.;
MVP
MPC
0.59
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at