19-16831631-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4_StrongBP6_ModerateBS2

The NM_001297595.2(SIN3B):c.365C>T(p.Ser122Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00162 in 1,613,928 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0017 ( 4 hom. )

Consequence

SIN3B
NM_001297595.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.67

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PP2

Missense variant where missense usually causes diseases, SIN3B

BP4

Computational evidence support a benign effect (MetaRNN=0.010037929).

BP6

Variant 19-16831631-C-T is Benign according to our data. Variant chr19-16831631-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3040879.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 176 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIN3B	NM_001297595.2 linkuse as main transcript	c.365C>T	p.Ser122Leu	missense_variant	3/19	ENST00000248054.10
SIN3B	NM_015260.4 linkuse as main transcript	c.365C>T	p.Ser122Leu	missense_variant	3/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIN3B	ENST00000248054.10 linkuse as main transcript	c.365C>T	p.Ser122Leu	missense_variant	3/19	1	NM_001297595.2	P1	O75182-2
SIN3B	ENST00000379803.5 linkuse as main transcript	c.365C>T	p.Ser122Leu	missense_variant	3/20	1			O75182-1
SIN3B	ENST00000596802.5 linkuse as main transcript	c.365C>T	p.Ser122Leu	missense_variant	3/8	1			O75182-3

Frequencies

GnomAD3 genomes

AF:

0.00116

AC:

176

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000434

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00188

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00121

AC:

303

AN:

251440

Hom.:

AF XY:

0.00121

AC XY:

165

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00226

Gnomad NFE exome

AF:

0.00204

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00167

AC:

2445

AN:

1461660

Hom.:

Cov.:

AF XY:

0.00161

AC XY:

1171

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00236

Gnomad4 NFE exome

AF:

0.00201

Gnomad4 OTH exome

AF:

0.00108

GnomAD4 genome

AF:

0.00116

AC:

176

AN:

152268

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00188

Gnomad4 NFE

AF:

0.00188

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00161

Hom.:

Bravo

AF:

0.000945

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00209

AC:

ExAC

AF:

0.00139

AC:

169

EpiCase

AF:

0.00136

EpiControl

AF:

0.00136

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

SIN3B-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 11, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.44

Cadd

Uncertain

Dann

Uncertain

1.0

Eigen

Benign

0.070

Eigen_PC

Benign

0.20

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Benign

0.021

MetaRNN

Benign

0.010

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

M;M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-2.1

N;.;N

REVEL

Benign

0.092

Sift

Uncertain

0.022

D;.;D

Sift4G

Benign

0.13

T;T;T

Polyphen

0.39

B;B;B

Vest4

0.54

MVP

0.24

MPC

0.78

ClinPred

0.028

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.16

gMVP

0.70

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