chr4-107931741-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_183075.3(CYP2U1):c.98G>T(p.Ser33Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000323 in 1,422,572 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. S33S) has been classified as Likely benign.
Frequency
Consequence
NM_183075.3 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 |
---|---|---|---|---|---|---|---|
CYP2U1 | NM_183075.3 | c.98G>T | p.Ser33Ile | missense_variant | 1/5 | ENST00000332884.11 | |
CYP2U1-AS1 | NR_125929.1 | n.149+230C>A | intron_variant, non_coding_transcript_variant | ||||
LOC107986298 | XR_001741784.2 | n.205-21192C>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYP2U1 | ENST00000332884.11 | c.98G>T | p.Ser33Ile | missense_variant | 1/5 | 1 | NM_183075.3 | P1 | |
CYP2U1-AS1 | ENST00000656249.1 | n.81-21192C>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 151976Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000821 AC: 3AN: 36542Hom.: 0 AF XY: 0.0000965 AC XY: 2AN XY: 20736
GnomAD4 exome AF: 0.0000323 AC: 41AN: 1270488Hom.: 0 Cov.: 30 AF XY: 0.0000338 AC XY: 21AN XY: 621086
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152084Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74358
ClinVar
Submissions by phenotype
Spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 25, 2022 | This sequence change replaces serine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 33 of the CYP2U1 protein (p.Ser33Ile). This variant is present in population databases (no rsID available, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with CYP2U1-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CYP2U1 protein function. 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. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 14, 2023 | The c.98G>T (p.S33I) alteration is located in exon 1 (coding exon 1) of the CYP2U1 gene. This alteration results from a G to T substitution at nucleotide position 98, causing the serine (S) at amino acid position 33 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at