chr19-48918728-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_006184.6(NUCB1):āc.760A>Gā(p.Ile254Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000178 in 1,613,388 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_006184.6 missense, splice_region
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/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NUCB1 | NM_006184.6 | c.760A>G | p.Ile254Val | missense_variant, splice_region_variant | 8/13 | ENST00000405315.9 | NP_006175.2 | |
NUCB1-AS1 | NR_046633.1 | n.164T>C | non_coding_transcript_exon_variant | 1/2 | ||||
NUCB1 | XM_017026845.2 | c.760A>G | p.Ile254Val | missense_variant, splice_region_variant | 8/13 | XP_016882334.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NUCB1 | ENST00000405315.9 | c.760A>G | p.Ile254Val | missense_variant, splice_region_variant | 8/13 | 1 | NM_006184.6 | ENSP00000385923 | P2 | |
NUCB1-AS1 | ENST00000416432.1 | n.164T>C | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000171 AC: 26AN: 152100Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000107 AC: 27AN: 251468Hom.: 0 AF XY: 0.000125 AC XY: 17AN XY: 135906
GnomAD4 exome AF: 0.000179 AC: 261AN: 1461170Hom.: 0 Cov.: 31 AF XY: 0.000158 AC XY: 115AN XY: 726926
GnomAD4 genome AF: 0.000171 AC: 26AN: 152218Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7AN XY: 74428
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 30, 2022 | The c.760A>G (p.I254V) alteration is located in exon 8 (coding exon 7) of the NUCB1 gene. This alteration results from a A to G substitution at nucleotide position 760, causing the isoleucine (I) at amino acid position 254 to be replaced by a valine (V). 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