14-57274732-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018229.4(AP5M1):​c.563C>T​(p.Ser188Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. S188Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

AP5M1
NM_018229.4 missense

Scores

1
7
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.89
Variant links:
Genes affected
AP5M1 (HGNC:20192): (adaptor related protein complex 5 subunit mu 1) Involved in endosomal transport. Located in several cellular components, including cytosol; late endosome; and lysosome. Part of AP-type membrane coat adaptor complex. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AP5M1NM_018229.4 linkc.563C>T p.Ser188Phe missense_variant Exon 2 of 8 ENST00000261558.8 NP_060699.3 Q9H0R1-1A0A024R654
AP5M1XM_011536940.4 linkc.605C>T p.Ser202Phe missense_variant Exon 3 of 9 XP_011535242.1 E7EQ45
AP5M1NR_026895.2 linkn.418+5344C>T intron_variant Intron 1 of 6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AP5M1ENST00000261558.8 linkc.563C>T p.Ser188Phe missense_variant Exon 2 of 8 1 NM_018229.4 ENSP00000261558.3 Q9H0R1-1
AP5M1ENST00000431972.6 linkc.605C>T p.Ser202Phe missense_variant Exon 3 of 9 2 ENSP00000390531.2 E7EQ45

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.41
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.066
T;T
Eigen
Uncertain
0.49
Eigen_PC
Uncertain
0.47
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.80
T;T
M_CAP
Benign
0.052
D
MetaRNN
Uncertain
0.44
T;T
MetaSVM
Benign
-0.81
T
MutationAssessor
Uncertain
2.1
M;.
PrimateAI
Benign
0.40
T
PROVEAN
Uncertain
-2.8
D;D
REVEL
Benign
0.15
Sift
Uncertain
0.014
D;D
Sift4G
Benign
0.090
T;T
Polyphen
0.88
P;.
Vest4
0.36
MutPred
0.30
Loss of disorder (P = 0.0071);.;
MVP
0.74
MPC
0.26
ClinPred
0.94
D
GERP RS
5.8
Varity_R
0.12
gMVP
0.38

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs984970036; hg19: chr14-57741450; COSMIC: COSV55106940; COSMIC: COSV55106940; API