19-16829436-G-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.16G>A(p.Gly6Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000189 in 1,057,312 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: 31)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: SIN3B NM_001297595.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0280

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=0.08247614).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIN3B	NM_001297595.2	c.16G>A	p.Gly6Ser	missense_variant	1/19	ENST00000248054.10
SIN3B	NM_015260.4	c.16G>A	p.Gly6Ser	missense_variant	1/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIN3B	ENST00000248054.10	c.16G>A	p.Gly6Ser	missense_variant	1/19	1	NM_001297595.2	P1
SIN3B	ENST00000379803.5	c.16G>A	p.Gly6Ser	missense_variant	1/20	1
SIN3B	ENST00000596802.5	c.16G>A	p.Gly6Ser	missense_variant	1/8	1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000189 AC: 2 AN: 1057312 Hom.: 0 Cov.: 30 AF XY: 0.00000200 AC XY: 1 AN XY: 498936

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000221

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 08, 2023

The c.16G>A (p.G6S) alteration is located in exon 1 (coding exon 1) of the SIN3B gene. This alteration results from a G to A substitution at nucleotide position 16, causing the glycine (G) at amino acid position 6 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	0.17
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
Cadd	Benign	14
Dann	Benign	0.97
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.083	N
LIST_S2	Benign	0.50	T;T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.082	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.0	N;N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.11	N;.;N
REVEL	Benign	0.030
Sift	Benign	0.84	T;.;T
Sift4G	Benign	0.49	T;T;T
Polyphen		0.0090	B;.;P
Vest4		0.12
MutPred		0.27		Gain of glycosylation at G6 (P = 2e-04);Gain of glycosylation at G6 (P = 2e-04);Gain of glycosylation at G6 (P = 2e-04);
MVP		0.46
MPC		0.84
ClinPred		0.13	T
GERP RS		-0.091
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.038
gMVP		0.26

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

Other links and lift over

dbSNP: rs1305780381; hg19: chr19-16940247;