rs199814669
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP2BP4_StrongBP6_Very_StrongBS2
The NM_022455.5(NSD1):āc.3564G>Cā(p.Arg1188Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000368 in 1,609,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. R1188K) 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 -15 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NSD1 | NM_022455.5 | c.3564G>C | p.Arg1188Ser | missense_variant | 5/23 | ENST00000439151.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NSD1 | ENST00000439151.7 | c.3564G>C | p.Arg1188Ser | missense_variant | 5/23 | 1 | NM_022455.5 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000401 AC: 61AN: 152108Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000449 AC: 112AN: 249698Hom.: 0 AF XY: 0.000370 AC XY: 50AN XY: 135024
GnomAD4 exome AF: 0.000364 AC: 531AN: 1457764Hom.: 0 Cov.: 37 AF XY: 0.000353 AC XY: 256AN XY: 724718
GnomAD4 genome ? AF: 0.000401 AC: 61AN: 152108Hom.: 0 Cov.: 31 AF XY: 0.000390 AC XY: 29AN XY: 74290
ClinVar
Submissions by phenotype
Sotos syndrome Benign:3
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Oct 27, 2022 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Dec 28, 2021 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 05, 2016 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 29, 2017 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 05, 2019 | This variant is associated with the following publications: (PMID: 16247291) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at