rs74882337
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The ENST00000417368.7(AASS):c.1678C>T(p.Pro560Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00606 in 1,613,710 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0045 ( 3 hom., cov: 32)
Exomes 𝑓: 0.0062 ( 37 hom. )
Consequence
AASS
ENST00000417368.7 missense
ENST00000417368.7 missense
Scores
2
8
9
Clinical Significance
Conservation
PhyloP100: 7.69
Genes affected
AASS (HGNC:17366): (aminoadipate-semialdehyde synthase) This gene encodes a bifunctional enzyme that catalyzes the first two steps in the mammalian lysine degradation pathway. The N-terminal and the C-terminal portions of this enzyme contain lysine-ketoglutarate reductase and saccharopine dehydrogenase activity, respectively, resulting in the conversion of lysine to alpha-aminoadipic semialdehyde. Mutations in this gene are associated with familial hyperlysinemia. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
Variant 7-122093136-G-A is Benign according to our data. Variant chr7-122093136-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 377290.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-122093136-G-A is described in Lovd as [Likely_benign]. Variant chr7-122093136-G-A is described in Lovd as [Pathogenic].
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00449 (683/152236) while in subpopulation NFE AF= 0.00785 (534/68022). AF 95% confidence interval is 0.0073. There are 3 homozygotes in gnomad4. There are 312 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AASS | NM_005763.4 | c.1678C>T | p.Pro560Ser | missense_variant | 16/24 | ENST00000417368.7 | NP_005754.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AASS | ENST00000417368.7 | c.1678C>T | p.Pro560Ser | missense_variant | 16/24 | 1 | NM_005763.4 | ENSP00000403768 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00449 AC: 683AN: 152118Hom.: 3 Cov.: 32
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GnomAD3 exomes AF: 0.00384 AC: 964AN: 250956Hom.: 5 AF XY: 0.00364 AC XY: 493AN XY: 135606
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GnomAD4 exome AF: 0.00623 AC: 9098AN: 1461474Hom.: 37 Cov.: 32 AF XY: 0.00599 AC XY: 4355AN XY: 727060
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GnomAD4 genome AF: 0.00449 AC: 683AN: 152236Hom.: 3 Cov.: 32 AF XY: 0.00419 AC XY: 312AN XY: 74440
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ClinVar
Significance: Likely benign
Submissions summary: Uncertain:1Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:4
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | AASS: BS2 - |
Uncertain significance, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Mar 08, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Nov 07, 2016 | - - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 08, 2024 | - - |
AASS-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | May 09, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Hyperlysinemia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 20, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
P;P
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: -15
Find out detailed SpliceAI scores and Pangolin per-transcript scores at