rs147530082
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_017838.4(NHP2):āc.290T>Cā(p.Met97Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00013 in 1,613,838 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M97V) has been classified as Uncertain significance.
Frequency
Consequence
NM_017838.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NHP2 | NM_017838.4 | c.290T>C | p.Met97Thr | missense_variant | 3/4 | ENST00000274606.8 | |
NHP2 | NM_001396110.1 | c.290T>C | p.Met97Thr | missense_variant | 3/5 | ||
NHP2 | NM_001034833.2 | c.231-1096T>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NHP2 | ENST00000274606.8 | c.290T>C | p.Met97Thr | missense_variant | 3/4 | 1 | NM_017838.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152148Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251496Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135922
GnomAD4 exome AF: 0.000138 AC: 201AN: 1461690Hom.: 1 Cov.: 30 AF XY: 0.000143 AC XY: 104AN XY: 727148
GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152148Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74334
ClinVar
Submissions by phenotype
Dyskeratosis congenita Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 19, 2022 | This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 97 of the NHP2 protein (p.Met97Thr). This variant is present in population databases (rs147530082, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with NHP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 570667). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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