20-45883654-C-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_080603.5(ZSWIM1):c.1062C>A(p.His354Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000266 in 1,614,102 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H354Y) has been classified as Uncertain significance.
Frequency
Consequence
NM_080603.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ZSWIM1 | NM_080603.5 | c.1062C>A | p.His354Gln | missense_variant | Exon 2 of 2 | ENST00000372523.1 | NP_542170.3 | |
ZSWIM1 | XM_005260610.6 | c.1062C>A | p.His354Gln | missense_variant | Exon 2 of 2 | XP_005260667.1 | ||
ZSWIM1 | XM_005260611.5 | c.1062C>A | p.His354Gln | missense_variant | Exon 2 of 2 | XP_005260668.1 | ||
ZSWIM1 | XM_011529100.3 | c.1062C>A | p.His354Gln | missense_variant | Exon 2 of 2 | XP_011527402.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152224Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000147 AC: 37AN: 251408Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135876
GnomAD4 exome AF: 0.0000267 AC: 39AN: 1461878Hom.: 0 Cov.: 34 AF XY: 0.0000220 AC XY: 16AN XY: 727240
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152224Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74378
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.1062C>A (p.H354Q) alteration is located in exon 2 (coding exon 1) of the ZSWIM1 gene. This alteration results from a C to A substitution at nucleotide position 1062, causing the histidine (H) at amino acid position 354 to be replaced by a glutamine (Q). 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