chrX-21737670-TCTC-T
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PM4_Supporting
The NM_014332.3(SMPX):c.157_159del(p.Glu53del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00000182 in 1,097,067 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 23)
Exomes 𝑓: 0.0000018 ( 0 hom. 0 hem. )
Consequence
SMPX
NM_014332.3 inframe_deletion
NM_014332.3 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.07
Genes affected
SMPX (HGNC:11122): (small muscle protein X-linked) This gene encodes a small protein that has no known functional domains. Mutations in this gene are a cause of X-linked deafness-4, and the encoded protein may play a role in the maintenance of inner ear cells subjected to mechanical stress. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Dec 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM1
?
In a chain Small muscular protein (size 87) in uniprot entity SMPX_HUMAN there are 4 pathogenic changes around while only 1 benign (80%) in NM_014332.3
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Nonframeshift variant in NON repetitive region in NM_014332.3. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMPX | NM_014332.3 | c.157_159del | p.Glu53del | inframe_deletion | 4/5 | ENST00000379494.4 | |
SMPX | XM_047441939.1 | c.157_159del | p.Glu53del | inframe_deletion | 4/7 | ||
SMPX | XM_047441940.1 | c.157_159del | p.Glu53del | inframe_deletion | 4/5 | ||
SMPX | NR_045617.2 | n.344_346del | non_coding_transcript_exon_variant | 4/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMPX | ENST00000379494.4 | c.157_159del | p.Glu53del | inframe_deletion | 4/5 | 1 | NM_014332.3 | P1 | |
SMPX | ENST00000646008.1 | c.157_159del | p.Glu53del | inframe_deletion | 4/5 | P1 | |||
SMPX | ENST00000494525.1 | c.157_159del | p.Glu53del | inframe_deletion, NMD_transcript_variant | 4/6 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
GnomAD4 exome AF: 0.00000182 AC: 2AN: 1097067Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 362473
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GnomAD4 genome ? Cov.: 23
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23
Bravo
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2023 | This variant, c.157_159del, results in the deletion of 1 amino acid(s) of the SMPX protein (p.Glu53del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SMPX-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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
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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