Variant 19-16829807-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_001297595.2(SIN3B):c.137C>G(p.Thr46Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SIN3B
NM_001297595.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.66

Variant links:

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]

SIN3B links:

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ACMG classification

Classification made for transcript

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=0.11926547).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIN3B	NM_001297595.2 linkuse as main transcript	c.137C>G	p.Thr46Ser	missense_variant	2/19	ENST00000248054.10
SIN3B	NM_015260.4 linkuse as main transcript	c.137C>G	p.Thr46Ser	missense_variant	2/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIN3B	ENST00000248054.10 linkuse as main transcript	c.137C>G	p.Thr46Ser	missense_variant	2/19	1	NM_001297595.2	P1	O75182-2
SIN3B	ENST00000379803.5 linkuse as main transcript	c.137C>G	p.Thr46Ser	missense_variant	2/20	1			O75182-1
SIN3B	ENST00000596802.5 linkuse as main transcript	c.137C>G	p.Thr46Ser	missense_variant	2/8	1			O75182-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250324

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135526

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460870

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726746

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

ExAC

AF:

0.00000824

AC:

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

Jun 21, 2023

The c.137C>G (p.T46S) alteration is located in exon 2 (coding exon 2) of the SIN3B gene. This alteration results from a C to G substitution at nucleotide position 137, causing the threonine (T) at amino acid position 46 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.88

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.22

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.74

T;T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.4

N;N;N

MutationTaster

Benign

0.79

D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

1.6

N;.;N

REVEL

Benign

0.13

Sift

Benign

1.0

T;.;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;.;B

Vest4

0.16

MutPred

0.30

Gain of disorder (P = 0.1899);Gain of disorder (P = 0.1899);Gain of disorder (P = 0.1899);

MVP

0.18

MPC

0.76

ClinPred

0.16

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.28

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over