Variant rs999885 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004722.4(AP4M1):c.462+34G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 1,613,518 control chromosomes in the GnomAD database, including 229,167 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 18579 hom., cov: 31)

Exomes 𝑓: 0.53 ( 210588 hom. )

Consequence

AP4M1
NM_004722.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.532

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]

AP4M1 links:

AP4M1 (HGNC:):

AP4M1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 7-100103553-G-A is Benign according to our data. Variant chr7-100103553-G-A is described in ClinVar as [Benign]. Clinvar id is 678005.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AP4M1	NM_004722.4 linkuse as main transcript	c.462+34G>A		intron_variant		ENST00000359593.9	NP_004713.2	O00189

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AP4M1	ENST00000359593.9 linkuse as main transcript	c.462+34G>A		intron_variant		1	NM_004722.4	ENSP00000352603.4		O00189

Frequencies

GnomAD3 genomes

AF:

0.474

AC:

72051

AN:

151894

Hom.:

18569

Cov.:

show subpopulations

Gnomad AFR

AF:

0.278

Gnomad AMI

AF:

0.507

Gnomad AMR

AF:

0.571

Gnomad ASJ

AF:

0.600

Gnomad EAS

AF:

0.822

Gnomad SAS

AF:

0.650

Gnomad FIN

AF:

0.541

Gnomad MID

AF:

0.576

Gnomad NFE

AF:

0.515

Gnomad OTH

AF:

0.505

GnomAD3 exomes

AF:

0.558

AC:

140229

AN:

251472

Hom.:

40835

AF XY:

0.563

AC XY:

76563

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.275

Gnomad AMR exome

AF:

0.614

Gnomad ASJ exome

AF:

0.597

Gnomad EAS exome

AF:

0.835

Gnomad SAS exome

AF:

0.639

Gnomad FIN exome

AF:

0.538

Gnomad NFE exome

AF:

0.515

Gnomad OTH exome

AF:

0.555

GnomAD4 exome

AF:

0.531

AC:

776684

AN:

1461506

Hom.:

210588

Cov.:

AF XY:

0.536

AC XY:

389706

AN XY:

727098

show subpopulations

Gnomad4 AFR exome

AF:

0.266

Gnomad4 AMR exome

AF:

0.611

Gnomad4 ASJ exome

AF:

0.593

Gnomad4 EAS exome

AF:

0.823

Gnomad4 SAS exome

AF:

0.641

Gnomad4 FIN exome

AF:

0.532

Gnomad4 NFE exome

AF:

0.515

Gnomad4 OTH exome

AF:

0.538

GnomAD4 genome

AF:

0.474

AC:

72094

AN:

152012

Hom.:

18579

Cov.:

AF XY:

0.484

AC XY:

35976

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.278

Gnomad4 AMR

AF:

0.571

Gnomad4 ASJ

AF:

0.600

Gnomad4 EAS

AF:

0.821

Gnomad4 SAS

AF:

0.651

Gnomad4 FIN

AF:

0.541

Gnomad4 NFE

AF:

0.515

Gnomad4 OTH

AF:

0.509

Alfa

AF:

0.514

Hom.:

8763

Bravo

AF:

0.470

Asia WGS

AF:

0.713

AC:

2481

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Hereditary spastic paraplegia 50

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

Hereditary spastic paraplegia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Dec 12, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.1

DANN

Benign

0.37

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