rs752282553
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000435.3(NOTCH3):c.3524G>C(p.Arg1175Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,848 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R1175W) has been classified as Likely benign.
Frequency
Consequence
NM_000435.3 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 |
---|---|---|---|---|---|---|---|
NOTCH3 | NM_000435.3 | c.3524G>C | p.Arg1175Pro | missense_variant | 22/33 | ENST00000263388.7 | |
NOTCH3 | XM_005259924.5 | c.3368G>C | p.Arg1123Pro | missense_variant | 21/32 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOTCH3 | ENST00000263388.7 | c.3524G>C | p.Arg1175Pro | missense_variant | 22/33 | 1 | NM_000435.3 | P1 | |
NOTCH3 | ENST00000601011.1 | c.3365G>C | p.Arg1122Pro | missense_variant | 21/23 | 5 | |||
NOTCH3 | ENST00000595045.1 | n.360G>C | non_coding_transcript_exon_variant | 2/3 | 2 | ||||
NOTCH3 | ENST00000600841.1 | n.2G>C | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152186Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461662Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0AN XY: 727110
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152186Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74340
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jan 10, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at