19-16851427-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2

The NM_001297595.2(SIN3B):c.742C>T(p.Pro248Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000374 in 1,603,502 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

SIN3B
NM_001297595.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.71

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 Likely_benign. Variant got -5 ACMG points.

PP2

Missense variant where missense usually causes diseases, SIN3B

BP4

Computational evidence support a benign effect (MetaRNN=0.0798814).

BS2

High AC in GnomAdExome at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIN3B	NM_001297595.2 linkuse as main transcript	c.742C>T	p.Pro248Ser	missense_variant	6/19	ENST00000248054.10
SIN3B	NM_015260.4 linkuse as main transcript	c.742C>T	p.Pro248Ser	missense_variant	6/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIN3B	ENST00000248054.10 linkuse as main transcript	c.742C>T	p.Pro248Ser	missense_variant	6/19	1	NM_001297595.2	P1	O75182-2
SIN3B	ENST00000379803.5 linkuse as main transcript	c.742C>T	p.Pro248Ser	missense_variant	6/20	1			O75182-1
SIN3B	ENST00000596802.5 linkuse as main transcript	c.742C>T	p.Pro248Ser	missense_variant	6/8	1			O75182-3
SIN3B	ENST00000596638.1 linkuse as main transcript	c.178C>T	p.Pro60Ser	missense_variant	3/7	5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000248

AC:

AN:

241720

Hom.:

AF XY:

0.00000763

AC XY:

AN XY:

131092

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000345

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000345

AC:

AN:

1451254

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

721436

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000129

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000264

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

May 18, 2023

The c.742C>T (p.P248S) alteration is located in exon 6 (coding exon 6) of the SIN3B gene. This alteration results from a C to T substitution at nucleotide position 742, causing the proline (P) at amino acid position 248 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

0.085

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.44

Cadd

Benign

Dann

Benign

0.90

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.59

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.82

T;T;T

M_CAP

Benign

0.0059

MetaRNN

Benign

0.080

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;L;L

MutationTaster

Benign

0.94

N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.93

N;.;N

REVEL

Benign

0.062

Sift

Benign

0.34

T;.;T

Sift4G

Benign

0.67

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.42

MutPred

0.18

Loss of catalytic residue at P248 (P = 0.0494);Loss of catalytic residue at P248 (P = 0.0494);Loss of catalytic residue at P248 (P = 0.0494);

MVP

0.33

MPC

0.86

ClinPred

0.023

GERP RS

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.024

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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