Genetic Variant AP1M1:p.Leu114Leu (chr19-16208093-G-C) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_032493.4(AP1M1):c.342G>C(p.Leu114Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00628 in 1,613,898 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0045 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0065 ( 47 hom. )

Consequence

AP1M1
NM_032493.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.17

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]

AP1M1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 19-16208093-G-C is Benign according to our data. Variant chr19-16208093-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2649508.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.17 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AP1M1	NM_032493.4 link	c.342G>C	p.Leu114Leu	synonymous_variant	Exon 4 of 12	ENST00000291439.8	NP_115882.1	Q9BXS5-1A0A024R7K8B3KNH5
AP1M1	NM_001130524.2 link	c.342G>C	p.Leu114Leu	synonymous_variant	Exon 4 of 13		NP_001123996.1	Q9BXS5-2Q59EK3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP1M1	ENST00000291439.8 link	c.342G>C	p.Leu114Leu	synonymous_variant	Exon 4 of 12	1	NM_032493.4	ENSP00000291439.2		Q9BXS5-1

Frequencies

GnomAD3 genomes

AF:

0.00454

AC:

691

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000721

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.000623

Gnomad FIN

AF:

0.0198

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00593

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00499

AC:

1255

AN:

251394

Hom.:

AF XY:

0.00486

AC XY:

660

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.000923

Gnomad AMR exome

AF:

0.00113

Gnomad ASJ exome

AF:

0.00268

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00183

Gnomad FIN exome

AF:

0.0204

Gnomad NFE exome

AF:

0.00559

Gnomad OTH exome

AF:

0.00636

GnomAD4 exome

AF:

0.00646

AC:

9439

AN:

1461698

Hom.:

Cov.:

AF XY:

0.00631

AC XY:

4589

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.000747

Gnomad4 AMR exome

AF:

0.00107

Gnomad4 ASJ exome

AF:

0.00341

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00179

Gnomad4 FIN exome

AF:

0.0202

Gnomad4 NFE exome

AF:

0.00685

Gnomad4 OTH exome

AF:

0.00697

GnomAD4 genome

AF:

0.00454

AC:

691

AN:

152200

Hom.:

Cov.:

AF XY:

0.00485

AC XY:

361

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.00106

Gnomad4 AMR

AF:

0.000720

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.0198

Gnomad4 NFE

AF:

0.00593

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00477

Hom.:

Bravo

AF:

0.00318

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00595

EpiControl

AF:

0.00539

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, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

8.2

DANN

Benign

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over