chrX-21737681-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM1BP4_Moderate
The NM_014332.3(SMPX):c.149C>T(p.Ser50Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000141 in 1,208,620 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts 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. S50S) has been classified as Likely benign.
Frequency
Consequence
NM_014332.3 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 |
---|---|---|---|---|---|---|---|
SMPX | NM_014332.3 | c.149C>T | p.Ser50Leu | missense_variant | 4/5 | ENST00000379494.4 | |
SMPX | XM_047441939.1 | c.149C>T | p.Ser50Leu | missense_variant | 4/7 | ||
SMPX | XM_047441940.1 | c.149C>T | p.Ser50Leu | missense_variant | 4/5 | ||
SMPX | NR_045617.2 | n.336C>T | non_coding_transcript_exon_variant | 4/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMPX | ENST00000379494.4 | c.149C>T | p.Ser50Leu | missense_variant | 4/5 | 1 | NM_014332.3 | P1 | |
SMPX | ENST00000646008.1 | c.149C>T | p.Ser50Leu | missense_variant | 4/5 | P1 | |||
SMPX | ENST00000494525.1 | c.149C>T | p.Ser50Leu | missense_variant, NMD_transcript_variant | 4/6 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000447 AC: 5AN: 111874Hom.: 0 Cov.: 23 AF XY: 0.0000294 AC XY: 1AN XY: 34054
GnomAD3 exomes AF: 0.0000164 AC: 3AN: 183099Hom.: 0 AF XY: 0.0000148 AC XY: 1AN XY: 67663
GnomAD4 exome AF: 0.0000109 AC: 12AN: 1096746Hom.: 0 Cov.: 29 AF XY: 0.0000110 AC XY: 4AN XY: 362190
GnomAD4 genome ? AF: 0.0000447 AC: 5AN: 111874Hom.: 0 Cov.: 23 AF XY: 0.0000294 AC XY: 1AN XY: 34054
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 06, 2024 | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 50 of the SMPX protein (p.Ser50Leu). This variant is present in population databases (rs760877167, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with SMPX-related conditions. ClinVar contains an entry for this variant (Variation ID: 1983808). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at