6-32195753-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004557.4(NOTCH4):c.5696G>C(p.Ser1899Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_004557.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NOTCH4 | NM_004557.4 | c.5696G>C | p.Ser1899Thr | missense_variant | Exon 30 of 30 | ENST00000375023.3 | NP_004548.3 | |
NOTCH4 | NR_134949.2 | n.5404G>C | non_coding_transcript_exon_variant | Exon 30 of 30 | ||||
NOTCH4 | NR_134950.2 | n.5302G>C | non_coding_transcript_exon_variant | Exon 29 of 29 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NOTCH4 | ENST00000375023.3 | c.5696G>C | p.Ser1899Thr | missense_variant | Exon 30 of 30 | 1 | NM_004557.4 | ENSP00000364163.3 | ||
NOTCH4 | ENST00000474612.1 | n.4357G>C | non_coding_transcript_exon_variant | Exon 10 of 10 | 5 | |||||
NOTCH4 | ENST00000491215.1 | n.722G>C | non_coding_transcript_exon_variant | Exon 2 of 2 | 3 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.5696G>C (p.S1899T) alteration is located in exon 30 (coding exon 30) of the NOTCH4 gene. This alteration results from a G to C substitution at nucleotide position 5696, causing the serine (S) at amino acid position 1899 to be replaced by a threonine (T). 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