Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_014855.3(AP5Z1):c.1536G>A(p.Pro512Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000519 in 1,579,130 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. P512P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000053 ( 0 hom. )

Consequence

AP5Z1
NM_014855.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -6.34

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

hereditary spastic paraplegia
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
hereditary spastic paraplegia 48
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

AP5Z1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 7-4788235-G-A is Benign according to our data. Variant chr7-4788235-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 487225.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-6.34 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014855.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
AP5Z1	NM_014855.3	MANE Select	c.1536G>A	p.Pro512Pro	synonymous	Exon 12 of 17	NP_055670.1
AP5Z1	NM_001364858.1		c.1068G>A	p.Pro356Pro	synonymous	Exon 11 of 16	NP_001351787.1
AP5Z1	NR_157345.1		n.1667G>A		non_coding_transcript_exon	Exon 12 of 17

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
AP5Z1	ENST00000649063.2	MANE Select	c.1536G>A	p.Pro512Pro	synonymous	Exon 12 of 17	ENSP00000497815.1
AP5Z1	ENST00000650581.1		c.336G>A	p.Pro112Pro	synonymous	Exon 3 of 7	ENSP00000497156.1
AP5Z1	ENST00000469614.1	TSL:2	n.10G>A		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000724

AC:

AN:

193452

AF XY:

0.0000572

show subpopulations

Gnomad AFR exome

AF:

0.0000934

Gnomad AMR exome

AF:

0.000208

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000599

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000533

AC:

AN:

1427036

Hom.:

Cov.:

AF XY:

0.0000523

AC XY:

AN XY:

706844

show subpopulations

African (AFR)

AF:

0.0000916

AC:

AN:

32756

American (AMR)

AF:

0.000176

AC:

AN:

39852

Ashkenazi Jewish (ASJ)

AF:

0.000157

AC:

AN:

25504

East Asian (EAS)

AF:

0.0000264

AC:

AN:

37852

South Asian (SAS)

AF:

0.000196

AC:

AN:

81444

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50056

Middle Eastern (MID)

AF:

0.000215

AC:

AN:

4660

European-Non Finnish (NFE)

AF:

0.0000374

AC:

AN:

1095924

Other (OTH)

AF:

0.0000509

AC:

AN:

58988

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152094

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41432

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

67984

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000579

Hom.:

Bravo

AF:

0.0000642

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hereditary spastic paraplegia 48 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.15

(source)

DANN

Benign

0.90

PhyloP100

-6.3

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over