rs140990611
Positions:
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BS1BS2_Supporting
The NM_001171613.2(PREPL):c.940A>T(p.Asn314Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000331 in 1,613,976 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0017 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00019 ( 2 hom. )
Consequence
PREPL
NM_001171613.2 missense
NM_001171613.2 missense
Scores
7
10
Clinical Significance
Conservation
PhyloP100: 3.60
Genes affected
PREPL (HGNC:30228): (prolyl endopeptidase like) The protein encoded by this gene belongs to the prolyl oligopeptidase subfamily of serine peptidases. Mutations in this gene have been associated with hypotonia-cystinuria syndrome, also known as the 2p21 deletion syndrome. Several alternatively spliced transcript variants encoding either the same or different isoforms have been described for this gene.[provided by RefSeq, Jan 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.012288243).
BP6
?
Variant 2-44332605-T-A is Benign according to our data. Variant chr2-44332605-T-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 436416.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0017 (259/152306) while in subpopulation AFR AF= 0.00585 (243/41560). AF 95% confidence interval is 0.00524. There are 0 homozygotes in gnomad4. There are 133 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 2 AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PREPL | NM_001171613.2 | c.940A>T | p.Asn314Tyr | missense_variant | 8/14 | ENST00000409411.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PREPL | ENST00000409411.6 | c.940A>T | p.Asn314Tyr | missense_variant | 8/14 | 1 | NM_001171613.2 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00171 AC: 260AN: 152188Hom.: 0 Cov.: 32
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?
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GnomAD3 exomes AF: 0.000462 AC: 116AN: 251316Hom.: 1 AF XY: 0.000331 AC XY: 45AN XY: 135832
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GnomAD4 exome AF: 0.000188 AC: 275AN: 1461670Hom.: 2 Cov.: 30 AF XY: 0.000169 AC XY: 123AN XY: 727170
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GnomAD4 genome ? AF: 0.00170 AC: 259AN: 152306Hom.: 0 Cov.: 32 AF XY: 0.00179 AC XY: 133AN XY: 74488
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ESP6500AA
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3478
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 13, 2016 | - - |
Myasthenic syndrome, congenital, 22 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 22, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;.;.;.;.;.;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;N;N;N;N;N;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N;N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D;D;D;D;D;T
Sift4G
Uncertain
D;D;D;D;D;D;D;D
Polyphen
0.98, 0.98
.;.;.;D;D;D;D;D
Vest4
MVP
MPC
0.014
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at