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GeneBe

9-94928511-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001193329.3(AOPEP):c.1641C>T(p.Pro547=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000402 in 1,550,704 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00042 ( 8 hom. )

Consequence

AOPEP
NM_001193329.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.96
Variant links:
Genes affected
AOPEP (HGNC:1361): (aminopeptidase O (putative)) This gene encodes a member of the M1 zinc aminopeptidase family. The encoded protein is a zinc-dependent metallopeptidase that catalyzes the removal of an amino acid from the amino terminus of a protein or peptide. This protein may play a role in the generation of angiotensin IV. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 9-94928511-C-T is Benign according to our data. Variant chr9-94928511-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3025026.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-3.96 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000276 (42/152280) while in subpopulation SAS AF= 0.00789 (38/4816). AF 95% confidence interval is 0.00591. There are 0 homozygotes in gnomad4. There are 27 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAdExome at 4 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AOPEPNM_001193329.3 linkuse as main transcriptc.1641C>T p.Pro547= synonymous_variant 7/17 ENST00000375315.8
LOC101928119NR_147614.1 linkuse as main transcriptn.468G>A non_coding_transcript_exon_variant 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AOPEPENST00000375315.8 linkuse as main transcriptc.1641C>T p.Pro547= synonymous_variant 7/171 NM_001193329.3 P1Q8N6M6-1
ENST00000439872.1 linkuse as main transcript downstream_gene_variant 3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000276
AC:
42
AN:
152162
Hom.:
0
Cov.:
32
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:
0.00788
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00100
AC:
151
AN:
150988
Hom.:
4
AF XY:
0.00141
AC XY:
114
AN XY:
80874
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000278
Gnomad SAS exome
AF:
0.00635
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000534
Gnomad OTH exome
AF:
0.000451
GnomAD4 exome
AF:
0.000415
AC:
581
AN:
1398424
Hom.:
8
Cov.:
30
AF XY:
0.000607
AC XY:
419
AN XY:
689734
show subpopulations
Gnomad4 AFR exome
AF:
0.0000633
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000839
Gnomad4 SAS exome
AF:
0.00625
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000399
Gnomad4 OTH exome
AF:
0.000619
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000276
AC:
42
AN:
152280
Hom.:
0
Cov.:
32
AF XY:
0.000363
AC XY:
27
AN XY:
74456
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:
0.00789
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000843
Hom.:
0
Bravo
AF:
0.0000453
Asia WGS
AF:
0.00404
AC:
14
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenMar 01, 2024AOPEP: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
Cadd
Benign
0.078
Dann
Benign
0.85
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs545129535; hg19: chr9-97690793; API