chr14-73279391-G-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001005743.2(NUMB):c.1130C>T(p.Ala377Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000218 in 1,601,832 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A377D) has been classified as Uncertain significance.
Frequency
Consequence
NM_001005743.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NUMB | NM_001005743.2 | c.1130C>T | p.Ala377Val | missense_variant | 12/13 | ENST00000555238.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NUMB | ENST00000555238.6 | c.1130C>T | p.Ala377Val | missense_variant | 12/13 | 1 | NM_001005743.2 | P4 |
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152258Hom.: 0 Cov.: 31
GnomAD4 exome AF: 0.0000117 AC: 17AN: 1449574Hom.: 0 Cov.: 31 AF XY: 0.00000972 AC XY: 7AN XY: 720450
GnomAD4 genome AF: 0.000118 AC: 18AN: 152258Hom.: 0 Cov.: 31 AF XY: 0.000108 AC XY: 8AN XY: 74386
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 01, 2023 | The c.1130C>T (p.A377V) alteration is located in exon 12 (coding exon 9) of the NUMB gene. This alteration results from a C to T substitution at nucleotide position 1130, causing the alanine (A) at amino acid position 377 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