rs939213590
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001101426.4(CRPPA):āc.226C>Gā(p.Leu76Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000116 in 1,298,676 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Genomes: š 0.000059 ( 0 hom., cov: 33)
Exomes š: 0.0000052 ( 0 hom. )
Consequence
CRPPA
NM_001101426.4 missense
NM_001101426.4 missense
Scores
4
8
7
Clinical Significance
Conservation
PhyloP100: 6.65
Genes affected
CRPPA (HGNC:37276): (CDP-L-ribitol pyrophosphorylase A) This gene encodes a 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase-like protein. Mutations in this gene are the cause of Walker-Warburg syndrome. Alternate splicing results in multiple transcript variants. [provided by RefSeq, May 2012]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CRPPA | NM_001101426.4 | c.226C>G | p.Leu76Val | missense_variant | 1/10 | ENST00000407010.7 | |
LOC105375168 | XR_007060223.1 | n.297+115G>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CRPPA | ENST00000407010.7 | c.226C>G | p.Leu76Val | missense_variant | 1/10 | 5 | NM_001101426.4 | P1 | |
CRPPA | ENST00000399310.3 | c.226C>G | p.Leu76Val | missense_variant | 1/9 | 1 | |||
CRPPA | ENST00000674759.1 | c.-46-14760C>G | intron_variant | ||||||
CRPPA | ENST00000675257.1 | c.-46-14760C>G | intron_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000592 AC: 9AN: 152088Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.00000523 AC: 6AN: 1146588Hom.: 0 Cov.: 31 AF XY: 0.00000546 AC XY: 3AN XY: 549628
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GnomAD4 genome ? AF: 0.0000592 AC: 9AN: 152088Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5AN XY: 74300
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 01, 2017 | - - |
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7;C5190987:Autosomal recessive limb-girdle muscular dystrophy type 2U Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 24, 2021 | This sequence change replaces leucine with valine at codon 76 of the ISPD protein (p.Leu76Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has not been reported in the literature in individuals with ISPD-related conditions. ClinVar contains an entry for this variant (Variation ID: 435528). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Pathogenic
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
D;.
Vest4
MVP
MPC
ClinPred
D
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