7-4791348-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014855.3(AP5Z1):ā€‹c.2387G>Cā€‹(p.Arg796Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,608,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

AP5Z1
NM_014855.3 missense

Scores

8
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.23
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3899098).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
AP5Z1NM_014855.3 linkuse as main transcriptc.2387G>C p.Arg796Pro missense_variant 17/17 ENST00000649063.2 NP_055670.1 O43299-1
AP5Z1NM_001364858.1 linkuse as main transcriptc.1919G>C p.Arg640Pro missense_variant 16/16 NP_001351787.1
AP5Z1XM_047421098.1 linkuse as main transcriptc.2051G>C p.Arg684Pro missense_variant 15/15 XP_047277054.1
AP5Z1NR_157345.1 linkuse as main transcriptn.2518G>C non_coding_transcript_exon_variant 17/17

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
AP5Z1ENST00000649063.2 linkuse as main transcriptc.2387G>C p.Arg796Pro missense_variant 17/17 NM_014855.3 ENSP00000497815.1 O43299-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152270
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000424
AC:
1
AN:
235844
Hom.:
0
AF XY:
0.00000776
AC XY:
1
AN XY:
128942
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000952
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.87e-7
AC:
1
AN:
1456456
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
724106
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000253
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152270
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74388
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.42
BayesDel_addAF
Uncertain
0.046
T
BayesDel_noAF
Benign
-0.17
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.26
T;T
Eigen
Uncertain
0.35
Eigen_PC
Uncertain
0.26
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.77
.;T
M_CAP
Benign
0.028
D
MetaRNN
Benign
0.39
T;T
MetaSVM
Benign
-0.79
T
MutationAssessor
Uncertain
2.5
M;M
PrimateAI
Benign
0.34
T
PROVEAN
Uncertain
-2.8
D;.
REVEL
Benign
0.24
Sift
Benign
0.19
T;.
Sift4G
Benign
0.087
T;.
Polyphen
0.97
D;D
Vest4
0.75
MutPred
0.43
Loss of MoRF binding (P = 0.0011);Loss of MoRF binding (P = 0.0011);
MVP
0.21
ClinPred
0.87
D
GERP RS
2.3
Varity_R
0.43
gMVP
0.69

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: rs199981070; hg19: chr7-4830979; API