19-16228898-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_032493.4(AP1M1):​c.1017C>T​(p.Ser339Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000726 in 1,614,132 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00055 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00074 ( 1 hom. )

Consequence

AP1M1
NM_032493.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.688
Variant links:
Genes affected
AP1M1 (HGNC:13667): (adaptor related protein complex 1 subunit mu 1) The protein encoded by this gene is the medium chain of the trans-Golgi network clathrin-associated protein complex AP-1. The other components of this complex are beta-prime-adaptin, gamma-adaptin, and the small chain AP1S1. This complex is located at the Golgi vesicle and links clathrin to receptors in coated vesicles. These vesicles are involved in endocytosis and Golgi processing. Alternatively spliced transcript variants encoding distinct protein isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BP6
Variant 19-16228898-C-T is Benign according to our data. Variant chr19-16228898-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2649509.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.688 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AP1M1NM_032493.4 linkc.1017C>T p.Ser339Ser synonymous_variant Exon 9 of 12 ENST00000291439.8 NP_115882.1 Q9BXS5-1A0A024R7K8B3KNH5
AP1M1NM_001130524.2 linkc.1053C>T p.Ser351Ser synonymous_variant Exon 10 of 13 NP_001123996.1 Q9BXS5-2Q59EK3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AP1M1ENST00000291439.8 linkc.1017C>T p.Ser339Ser synonymous_variant Exon 9 of 12 1 NM_032493.4 ENSP00000291439.2 Q9BXS5-1

Frequencies

GnomAD3 genomes
AF:
0.000545
AC:
83
AN:
152160
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000265
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000376
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000926
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.000601
AC:
151
AN:
251318
Hom.:
0
AF XY:
0.000537
AC XY:
73
AN XY:
135860
show subpopulations
Gnomad AFR exome
AF:
0.000246
Gnomad AMR exome
AF:
0.0000578
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000598
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000324
Gnomad NFE exome
AF:
0.00104
Gnomad OTH exome
AF:
0.00147
GnomAD4 exome
AF:
0.000745
AC:
1089
AN:
1461854
Hom.:
1
Cov.:
30
AF XY:
0.000760
AC XY:
553
AN XY:
727232
show subpopulations
Gnomad4 AFR exome
AF:
0.000179
Gnomad4 AMR exome
AF:
0.0000894
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.000327
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000318
Gnomad4 NFE exome
AF:
0.000892
Gnomad4 OTH exome
AF:
0.000927
GnomAD4 genome
AF:
0.000545
AC:
83
AN:
152278
Hom.:
0
Cov.:
32
AF XY:
0.000470
AC XY:
35
AN XY:
74448
show subpopulations
Gnomad4 AFR
AF:
0.000265
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000194
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000376
Gnomad4 NFE
AF:
0.000926
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.000671
Hom.:
0
Bravo
AF:
0.000597
EpiCase
AF:
0.000927
EpiControl
AF:
0.000889

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Mar 01, 2023
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

AP1M1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.33
CADD
Benign
9.1
DANN
Benign
0.87
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs150468368; hg19: chr19-16339709; API