19-16829457-G-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_StrongBS2

The NM_001297595.2(SIN3B):c.37G>T(p.Ala13Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000987 in 1,215,468 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

SIN3B
NM_001297595.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.755

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 Benign. Variant got -7 ACMG points.

PP2

Missense variant where missense usually causes diseases, SIN3B

BP4

Computational evidence support a benign effect (MetaRNN=0.05482748).

BS2

High AC in GnomAd at 69 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIN3B	NM_001297595.2 linkuse as main transcript	c.37G>T	p.Ala13Ser	missense_variant	1/19	ENST00000248054.10
SIN3B	NM_015260.4 linkuse as main transcript	c.37G>T	p.Ala13Ser	missense_variant	1/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIN3B	ENST00000248054.10 linkuse as main transcript	c.37G>T	p.Ala13Ser	missense_variant	1/19	1	NM_001297595.2	P1	O75182-2
SIN3B	ENST00000379803.5 linkuse as main transcript	c.37G>T	p.Ala13Ser	missense_variant	1/20	1			O75182-1
SIN3B	ENST00000596802.5 linkuse as main transcript	c.37G>T	p.Ala13Ser	missense_variant	1/8	1			O75182-3

Frequencies

GnomAD3 genomes

AF:

0.000455

AC:

AN:

151802

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00152

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD4 exome

AF:

0.0000480

AC:

AN:

1063558

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

502064

show subpopulations

Gnomad4 AFR exome

AF:

0.00211

Gnomad4 AMR exome

AF:

0.000127

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000472

GnomAD4 genome

AF:

0.000454

AC:

AN:

151910

Hom.:

Cov.:

AF XY:

0.000431

AC XY:

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.00152

Gnomad4 AMR

AF:

0.000328

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000427

Hom.:

Bravo

AF:

0.000438

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, 2021

The c.37G>T (p.A13S) alteration is located in exon 1 (coding exon 1) of the SIN3B gene. This alteration results from a G to T substitution at nucleotide position 37, causing the alanine (A) at amino acid position 13 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

0.081

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.60

Cadd

Benign

6.2

Dann

Benign

0.81

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.22

T;T;T

M_CAP

Benign

0.026

MetaRNN

Benign

0.055

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

0.080

N;.;N

REVEL

Benign

0.025

Sift

Benign

0.80

T;.;T

Sift4G

Benign

0.46

T;T;T

Polyphen

0.088

.;.;B

Vest4

0.10

MutPred

0.21

Gain of glycosylation at A13 (P = 2e-04);Gain of glycosylation at A13 (P = 2e-04);Gain of glycosylation at A13 (P = 2e-04);

MVP

0.64

MPC

0.78

ClinPred

0.042

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.0

Varity_R

0.15

gMVP

0.17

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