19-16831628-A-G
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_001297595.2(SIN3B):c.362A>G(p.Gln121Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000805 in 1,613,946 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000075 ( 0 hom. )
Consequence
SIN3B
NM_001297595.2 missense
NM_001297595.2 missense
Scores
7
11
Clinical Significance
Conservation
PhyloP100: 5.61
Genes affected
SIN3B (HGNC:19354): (SIN3 transcription regulator family member B) Predicted to enable transcription corepressor activity. Predicted to be involved in histone deacetylation; negative regulation of transcription by RNA polymerase II; and striated muscle tissue development. Predicted to be located in nucleus. Predicted to be part of Sin3 complex. Predicted to be active in chromatin. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, SIN3B
BP4
?
Computational evidence support a benign effect (MetaRNN=0.18844318).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SIN3B | NM_001297595.2 | c.362A>G | p.Gln121Arg | missense_variant | 3/19 | ENST00000248054.10 | |
SIN3B | NM_015260.4 | c.362A>G | p.Gln121Arg | missense_variant | 3/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SIN3B | ENST00000248054.10 | c.362A>G | p.Gln121Arg | missense_variant | 3/19 | 1 | NM_001297595.2 | P1 | |
SIN3B | ENST00000379803.5 | c.362A>G | p.Gln121Arg | missense_variant | 3/20 | 1 | |||
SIN3B | ENST00000596802.5 | c.362A>G | p.Gln121Arg | missense_variant | 3/8 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152198Hom.: 0 Cov.: 31
GnomAD3 genomes
?
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GnomAD4 exome AF: 0.00000753 AC: 11AN: 1461748Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727188
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152198Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1AN XY: 74360
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 04, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with SIN3B-related conditions. This variant is present in population databases (rs368592710, gnomAD 0.007%). This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 121 of the SIN3B protein (p.Gln121Arg). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;N
REVEL
Benign
Sift
Benign
T;.;T
Sift4G
Benign
T;T;T
Polyphen
D;D;B
Vest4
MVP
MPC
0.98
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
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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