19-45940351-C-T
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_002516.4(NOVA2):c.991G>A(p.Ala331Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000456 in 1,336,300 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_002516.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NOVA2 | ENST00000263257.6 | c.991G>A | p.Ala331Thr | missense_variant | Exon 4 of 4 | 1 | NM_002516.4 | ENSP00000263257.4 | ||
NOVA2 | ENST00000676183.1 | c.1183G>A | p.Ala395Thr | missense_variant | Exon 4 of 4 | ENSP00000501708.1 |
Frequencies
GnomAD3 genomes AF: 0.0000736 AC: 11AN: 149506Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000122 AC: 6AN: 49246Hom.: 1 AF XY: 0.000101 AC XY: 3AN XY: 29614
GnomAD4 exome AF: 0.0000421 AC: 50AN: 1186794Hom.: 1 Cov.: 30 AF XY: 0.0000429 AC XY: 25AN XY: 582844
GnomAD4 genome AF: 0.0000736 AC: 11AN: 149506Hom.: 0 Cov.: 32 AF XY: 0.0000686 AC XY: 5AN XY: 72876
ClinVar
Submissions by phenotype
not provided Uncertain:1
NOVA2: PP2 -
Inborn genetic diseases Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at