rs772447375
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_022455.5(NSD1):c.2331A>C(p.Leu777=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000743 in 1,614,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000075 ( 0 hom. )
Consequence
NSD1
NM_022455.5 synonymous
NM_022455.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.84
Genes affected
NSD1 (HGNC:14234): (nuclear receptor binding SET domain protein 1) This gene encodes a protein containing a SET domain, 2 LXXLL motifs, 3 nuclear translocation signals (NLSs), 4 plant homeodomain (PHD) finger regions, and a proline-rich region. The encoded protein enhances androgen receptor (AR) transactivation, and this enhancement can be increased further in the presence of other androgen receptor associated coregulators. This protein may act as a nucleus-localized, basic transcriptional factor and also as a bifunctional transcriptional regulator. Mutations of this gene have been associated with Sotos syndrome and Weaver syndrome. One version of childhood acute myeloid leukemia is the result of a cryptic translocation with the breakpoints occurring within nuclear receptor-binding Su-var, enhancer of zeste, and trithorax domain protein 1 on chromosome 5 and nucleoporin, 98-kd on chromosome 11. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Sep 2018]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.97).
BP6
?
Variant 5-177210730-A-C is Benign according to our data. Variant chr5-177210730-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 414477.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High AC in GnomAdExome at 12 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NSD1 | NM_022455.5 | c.2331A>C | p.Leu777= | synonymous_variant | 5/23 | ENST00000439151.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NSD1 | ENST00000439151.7 | c.2331A>C | p.Leu777= | synonymous_variant | 5/23 | 1 | NM_022455.5 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152238Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000477 AC: 12AN: 251346Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135856
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GnomAD4 exome AF: 0.00000752 AC: 11AN: 1461866Hom.: 0 Cov.: 37 AF XY: 0.00000550 AC XY: 4AN XY: 727226
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152238Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74382
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 06, 2019 | 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. - |
Sotos syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 07, 2020 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
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Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at