14-57274732-C-G

Variant summary

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

The NM_018229.4(AP5M1):​c.563C>G​(p.Ser188Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
Exomes š‘“: 6.8e-7 ( 0 hom. )

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]

Genome browser will be placed here

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>G p.Ser188Cys missense_variant Exon 2 of 8 ENST00000261558.8 NP_060699.3 Q9H0R1-1A0A024R654
AP5M1XM_011536940.4 linkc.605C>G p.Ser202Cys missense_variant Exon 3 of 9 XP_011535242.1 E7EQ45
AP5M1NR_026895.2 linkn.418+5344C>G intron_variant Intron 1 of 6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AP5M1ENST00000261558.8 linkc.563C>G p.Ser188Cys missense_variant Exon 2 of 8 1 NM_018229.4 ENSP00000261558.3 Q9H0R1-1
AP5M1ENST00000431972.6 linkc.605C>G p.Ser202Cys missense_variant Exon 3 of 9 2 ENSP00000390531.2 E7EQ45

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461880
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727236
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
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
Benign
0.088
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
23
DANN
Uncertain
0.98
DEOGEN2
Benign
0.068
T;T
Eigen
Uncertain
0.54
Eigen_PC
Uncertain
0.50
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.73
T;T
M_CAP
Benign
0.039
D
MetaRNN
Uncertain
0.46
T;T
MetaSVM
Benign
-0.70
T
MutationAssessor
Uncertain
2.1
M;.
PrimateAI
Benign
0.38
T
PROVEAN
Uncertain
-2.6
D;D
REVEL
Benign
0.17
Sift
Uncertain
0.023
D;D
Sift4G
Benign
0.072
T;T
Polyphen
0.99
D;.
Vest4
0.35
MutPred
0.33
Loss of disorder (P = 0.0081);.;
MVP
0.78
MPC
0.38
ClinPred
0.97
D
GERP RS
5.8
Varity_R
0.10
gMVP
0.35

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: rs984970036; hg19: chr14-57741450; API