rs587777122

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5

The NM_005763.4(AASS):ā€‹c.874A>Gā€‹(p.Ile292Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000034 ( 0 hom. )

Consequence

AASS
NM_005763.4 missense

Scores

1
18

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 5.05
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 7-122116653-T-C is Pathogenic according to our data. Variant chr7-122116653-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 100643.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
AASSNM_005763.4 linkuse as main transcriptc.874A>G p.Ile292Val missense_variant 8/24 ENST00000417368.7 NP_005754.2 Q9UDR5A4D0W4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
AASSENST00000417368.7 linkuse as main transcriptc.874A>G p.Ile292Val missense_variant 8/241 NM_005763.4 ENSP00000403768.2 Q9UDR5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251150
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135724
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:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461804
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727200
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000307
Hom.:
0

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Hyperlysinemia Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMNov 01, 2013- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.061
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.40
CADD
Uncertain
24
DANN
Benign
0.89
DEOGEN2
Benign
0.20
T;T
Eigen
Benign
-0.31
Eigen_PC
Benign
-0.11
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.75
.;T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.18
T;T
MetaSVM
Benign
-0.61
T
MutationAssessor
Benign
1.1
L;L
PrimateAI
Benign
0.24
T
PROVEAN
Benign
0.050
N;N
REVEL
Benign
0.17
Sift
Benign
0.72
T;T
Sift4G
Benign
0.32
T;T
Polyphen
0.0
B;B
Vest4
0.16
MutPred
0.40
Loss of loop (P = 0.0804);Loss of loop (P = 0.0804);
MVP
0.66
MPC
0.12
ClinPred
0.16
T
GERP RS
4.7
Varity_R
0.036
gMVP
0.30

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.99
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.99
Position offset: 1

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: rs587777122; hg19: chr7-121756707; API