chr22-26443117-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_Strong
The NM_020437.5(ASPHD2):c.1021C>T(p.Arg341Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000452 in 1,613,968 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R341Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_020437.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ASPHD2 | NM_020437.5 | c.1021C>T | p.Arg341Trp | missense_variant | 4/4 | ENST00000215906.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ASPHD2 | ENST00000215906.6 | c.1021C>T | p.Arg341Trp | missense_variant | 4/4 | 1 | NM_020437.5 | P1 | |
HPS4 | ENST00000699226.1 | n.6459G>A | non_coding_transcript_exon_variant | 5/5 | |||||
HPS4 | ENST00000699228.1 | n.4083G>A | non_coding_transcript_exon_variant | 14/14 | |||||
HPS4 | ENST00000699227.1 | c.*2877G>A | 3_prime_UTR_variant, NMD_transcript_variant | 15/15 |
Frequencies
GnomAD3 genomes ? AF: 0.0000920 AC: 14AN: 152128Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251472Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135908
GnomAD4 exome AF: 0.0000404 AC: 59AN: 1461840Hom.: 0 Cov.: 30 AF XY: 0.0000358 AC XY: 26AN XY: 727232
GnomAD4 genome ? AF: 0.0000920 AC: 14AN: 152128Hom.: 0 Cov.: 31 AF XY: 0.0000404 AC XY: 3AN XY: 74312
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 21, 2023 | The c.1021C>T (p.R341W) alteration is located in exon 4 (coding exon 3) of the ASPHD2 gene. This alteration results from a C to T substitution at nucleotide position 1021, causing the arginine (R) at amino acid position 341 to be replaced by a tryptophan (W). 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