rs146262009

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_004722.4(AP4M1):ā€‹c.1012C>Gā€‹(p.Arg338Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. R338Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000041 ( 0 hom. )

Consequence

AP4M1
NM_004722.4 missense

Scores

5
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.07
Variant links:
Genes affected
AP4M1 (HGNC:574): (adaptor related protein complex 4 subunit mu 1) This gene encodes a subunit of the heterotetrameric AP-4 complex. The encoded protein belongs to the adaptor complexes medium subunits family. This AP-4 complex is involved in the recognition and sorting of cargo proteins with tyrosine-based motifs from the trans-golgi network to the endosomal-lysosomal system. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3316313).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AP4M1NM_004722.4 linkuse as main transcriptc.1012C>G p.Arg338Gly missense_variant 13/15 ENST00000359593.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AP4M1ENST00000359593.9 linkuse as main transcriptc.1012C>G p.Arg338Gly missense_variant 13/151 NM_004722.4 P3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251138
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135804
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000410
AC:
6
AN:
1461778
Hom.:
0
Cov.:
33
AF XY:
0.00000413
AC XY:
3
AN XY:
727190
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.29
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.18
T;T;.;.;.;.
Eigen
Benign
-0.028
Eigen_PC
Benign
0.042
FATHMM_MKL
Benign
0.75
D
LIST_S2
Uncertain
0.90
D;D;.;D;D;D
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.33
T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.1
.;.;L;L;.;.
MutationTaster
Benign
0.95
D;D;D;D
PrimateAI
Uncertain
0.51
T
PROVEAN
Uncertain
-3.7
D;D;D;D;D;D
REVEL
Benign
0.13
Sift
Benign
0.043
D;D;D;D;D;T
Sift4G
Uncertain
0.0070
D;T;T;T;D;D
Polyphen
0.52
.;P;P;P;.;.
Vest4
0.55, 0.55, 0.56
MutPred
0.48
.;Loss of solvent accessibility (P = 0.0044);.;.;.;.;
MVP
0.44
MPC
0.29
ClinPred
0.96
D
GERP RS
4.1
Varity_R
0.59
gMVP
0.37

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs146262009; hg19: chr7-99703901; API