X-152868898-T-C
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_015922.3(NSDHL):c.904T>C(p.Tyr302His) variant causes a missense change. The variant allele was found at a frequency of 0.00000826 in 1,210,534 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_015922.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NSDHL | NM_015922.3 | c.904T>C | p.Tyr302His | missense_variant | Exon 8 of 8 | ENST00000370274.8 | NP_057006.1 | |
NSDHL | NM_001129765.2 | c.904T>C | p.Tyr302His | missense_variant | Exon 9 of 9 | NP_001123237.1 | ||
NSDHL | XM_017029564.2 | c.952T>C | p.Tyr318His | missense_variant | Exon 8 of 8 | XP_016885053.1 | ||
NSDHL | XM_011531178.3 | c.904T>C | p.Tyr302His | missense_variant | Exon 10 of 10 | XP_011529480.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000889 AC: 1AN: 112503Hom.: 0 Cov.: 24 AF XY: 0.0000289 AC XY: 1AN XY: 34639
GnomAD3 exomes AF: 0.0000218 AC: 4AN: 183391Hom.: 0 AF XY: 0.0000147 AC XY: 1AN XY: 67833
GnomAD4 exome AF: 0.00000820 AC: 9AN: 1098031Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 1AN XY: 363385
GnomAD4 genome AF: 0.00000889 AC: 1AN: 112503Hom.: 0 Cov.: 24 AF XY: 0.0000289 AC XY: 1AN XY: 34639
ClinVar
Submissions by phenotype
not specified Uncertain:1
- -
not provided Uncertain:1
This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 302 of the NSDHL protein (p.Tyr302His). 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 436070). This variant has not been reported in the literature in individuals affected with NSDHL-related conditions. This variant is present in population databases (rs782181497, gnomAD 0.006%), including at least one homozygous and/or hemizygous individual. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at