chr19-16841852-G-C
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_001297595.2(SIN3B):c.466G>C(p.Glu156Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,974 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 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
SIN3B
NM_001297595.2 missense
NM_001297595.2 missense
Scores
1
3
14
Clinical Significance
Conservation
PhyloP100: 7.65
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=0.1666519).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SIN3B | NM_001297595.2 | c.466G>C | p.Glu156Gln | missense_variant | 4/19 | ENST00000248054.10 | |
SIN3B | NM_015260.4 | c.466G>C | p.Glu156Gln | missense_variant | 4/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SIN3B | ENST00000248054.10 | c.466G>C | p.Glu156Gln | missense_variant | 4/19 | 1 | NM_001297595.2 | P1 | |
SIN3B | ENST00000379803.5 | c.466G>C | p.Glu156Gln | missense_variant | 4/20 | 1 | |||
SIN3B | ENST00000596802.5 | c.466G>C | p.Glu156Gln | missense_variant | 4/8 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152086Hom.: 0 Cov.: 31
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251480Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135914
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GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461888Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727244
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GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152086Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74292
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 12, 2022 | The c.466G>C (p.E156Q) alteration is located in exon 4 (coding exon 4) of the SIN3B gene. This alteration results from a G to C substitution at nucleotide position 466, causing the glutamic acid (E) at amino acid position 156 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;N
REVEL
Benign
Sift
Benign
T;.;T
Sift4G
Benign
T;T;T
Polyphen
B;B;B
Vest4
MutPred
Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);
MVP
MPC
0.85
ClinPred
D
GERP RS
Varity_R
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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