rs373422736
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001101426.4(CRPPA):āc.990C>Gā(p.Ile330Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,611,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_001101426.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CRPPA | NM_001101426.4 | c.990C>G | p.Ile330Met | missense_variant | 7/10 | ENST00000407010.7 | |
CRPPA-AS1 | NR_038947.1 | n.241-7271G>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CRPPA | ENST00000407010.7 | c.990C>G | p.Ile330Met | missense_variant | 7/10 | 5 | NM_001101426.4 | P1 | |
CRPPA-AS1 | ENST00000438573.5 | n.222-2943G>C | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000658 AC: 10AN: 151972Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000162 AC: 4AN: 246782Hom.: 0 AF XY: 0.00000747 AC XY: 1AN XY: 133852
GnomAD4 exome AF: 0.00000617 AC: 9AN: 1459050Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 725724
GnomAD4 genome ? AF: 0.0000658 AC: 10AN: 151972Hom.: 0 Cov.: 33 AF XY: 0.0000674 AC XY: 5AN XY: 74216
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 09, 2021 | The c.990C>G (p.I330M) alteration is located in exon 7 (coding exon 7) of the ISPD gene. This alteration results from a C to G substitution at nucleotide position 990, causing the isoleucine (I) at amino acid position 330 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
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 | Aug 23, 2022 | This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 330 of the ISPD protein (p.Ile330Met). This variant is present in population databases (rs373422736, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with ISPD-related conditions. ClinVar contains an entry for this variant (Variation ID: 574208). 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; 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:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at