5-177135498-G-C
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP2BP4_ModerateBP6_Very_StrongBS2
The NM_022455.5(NSD1):āc.395G>Cā(p.Cys132Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000929 in 1,614,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C132Y) has been classified as Uncertain significance.
Frequency
Consequence
NM_022455.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NSD1 | NM_022455.5 | c.395G>C | p.Cys132Ser | missense_variant | 2/23 | ENST00000439151.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NSD1 | ENST00000439151.7 | c.395G>C | p.Cys132Ser | missense_variant | 2/23 | 1 | NM_022455.5 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000788 AC: 12AN: 152204Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000875 AC: 22AN: 251480Hom.: 0 AF XY: 0.0000809 AC XY: 11AN XY: 135918
GnomAD4 exome AF: 0.0000944 AC: 138AN: 1461892Hom.: 0 Cov.: 32 AF XY: 0.0000880 AC XY: 64AN XY: 727248
GnomAD4 genome AF: 0.0000788 AC: 12AN: 152204Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74372
ClinVar
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
Sotos syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 07, 2022 | - - |
NSD1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 20, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at