19-16846986-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_001297595.2(SIN3B):c.599C>A(p.Thr200Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SIN3B NM_001297595.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.89

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, SIN3B
• BP4: Computational evidence support a benign effect (MetaRNN=0.15778187).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIN3B	NM_001297595.2	c.599C>A	p.Thr200Lys	missense_variant	5/19	ENST00000248054.10
SIN3B	NM_015260.4	c.599C>A	p.Thr200Lys	missense_variant	5/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIN3B	ENST00000248054.10	c.599C>A	p.Thr200Lys	missense_variant	5/19	1	NM_001297595.2	P1
SIN3B	ENST00000379803.5	c.599C>A	p.Thr200Lys	missense_variant	5/20	1
SIN3B	ENST00000596802.5	c.599C>A	p.Thr200Lys	missense_variant	5/8	1
SIN3B	ENST00000596638.1	c.35C>A	p.Thr12Lys	missense_variant	2/7	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Aug 31, 2022

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
Cadd	Uncertain	24
Dann	Uncertain	0.98
Eigen	Benign	-0.12
Eigen_PC	Benign	0.016
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.82	T;T;T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M;M;M
MutationTaster	Benign	0.58	N;N
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.3	N;.;N
REVEL	Benign	0.050
Sift	Benign	0.95	T;.;T
Sift4G	Benign	0.48	T;T;T
Polyphen		0.58	P;P;B
Vest4		0.56
MutPred		0.42		Gain of methylation at T200 (P = 0.0387);Gain of methylation at T200 (P = 0.0387);Gain of methylation at T200 (P = 0.0387);
MVP		0.35
MPC		1.2
ClinPred		0.54	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-16957797;