Variant rs3750013 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_014855.3(AP5Z1):c.1596-66G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0722 in 1,385,678 control chromosomes in the GnomAD database, including 4,408 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.076 ( 511 hom., cov: 33)

Exomes 𝑓: 0.072 ( 3897 hom. )

Consequence

AP5Z1
NM_014855.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.62

Variant links:

Genes affected

AP5Z1 (HGNC:22197): (adaptor related protein complex 5 subunit zeta 1) This gene was identified by genome-wide screen for genes involved in homologous recombination DNA double-strand break repair (HR-DSBR). The encoded protein was found in a complex with other proteins that have a role in HR-DSBR. Knockdown of this gene reduced homologous recombination, and mutations in this gene were found in patients with spastic paraplegia. It was concluded that this gene likely encodes a helicase (PMID:20613862). [provided by RefSeq, Jan 2011]

AP5Z1 links:

AP5Z1 (HGNC:):

AP5Z1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

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

BP6

Variant 7-4788774-G-A is Benign according to our data. Variant chr7-4788774-G-A is described in ClinVar as [Benign]. Clinvar id is 1293090.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
AP5Z1	NM_014855.3 linkuse as main transcript	c.1596-66G>A	intron_variant	ENST00000649063.2	NP_055670.1	O43299-1
AP5Z1	NM_001364858.1 linkuse as main transcript	c.1128-66G>A	intron_variant		NP_001351787.1
AP5Z1	XM_047421098.1 linkuse as main transcript	c.1260-66G>A	intron_variant		XP_047277054.1
AP5Z1	NR_157345.1 linkuse as main transcript	n.1727-66G>A	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AP5Z1	ENST00000649063.2 linkuse as main transcript	c.1596-66G>A		intron_variant			NM_014855.3	ENSP00000497815.1		O43299-1

Frequencies

GnomAD3 genomes

AF:

0.0761

AC:

11568

AN:

152108

Hom.:

507

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0916

Gnomad AMI

AF:

0.106

Gnomad AMR

AF:

0.0499

Gnomad ASJ

AF:

0.145

Gnomad EAS

AF:

0.0616

Gnomad SAS

AF:

0.183

Gnomad FIN

AF:

0.0420

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0674

Gnomad OTH

AF:

0.0728

GnomAD4 exome

AF:

0.0717

AC:

88390

AN:

1233452

Hom.:

3897

Cov.:

AF XY:

0.0749

AC XY:

45247

AN XY:

604162

show subpopulations

Gnomad4 AFR exome

AF:

0.0917

Gnomad4 AMR exome

AF:

0.0389

Gnomad4 ASJ exome

AF:

0.138

Gnomad4 EAS exome

AF:

0.0757

Gnomad4 SAS exome

AF:

0.180

Gnomad4 FIN exome

AF:

0.0451

Gnomad4 NFE exome

AF:

0.0636

Gnomad4 OTH exome

AF:

0.0796

GnomAD4 genome

AF:

0.0761

AC:

11588

AN:

152226

Hom.:

511

Cov.:

AF XY:

0.0758

AC XY:

5643

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0920

Gnomad4 AMR

AF:

0.0498

Gnomad4 ASJ

AF:

0.145

Gnomad4 EAS

AF:

0.0615

Gnomad4 SAS

AF:

0.183

Gnomad4 FIN

AF:

0.0420

Gnomad4 NFE

AF:

0.0674

Gnomad4 OTH

AF:

0.0720

Alfa

AF:

0.0262

Hom.:

Bravo

AF:

0.0738

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.93

DANN

Benign

0.90

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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