19-16831537-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP2 BP4

The NM_001297595.2(SIN3B):c.271C>T(p.His91Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SIN3B NM_001297595.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.21

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 2 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=0.33873892).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIN3B	NM_001297595.2	c.271C>T	p.His91Tyr	missense_variant	3/19	ENST00000248054.10
SIN3B	NM_015260.4	c.271C>T	p.His91Tyr	missense_variant	3/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIN3B	ENST00000248054.10	c.271C>T	p.His91Tyr	missense_variant	3/19	1	NM_001297595.2	P1
SIN3B	ENST00000379803.5	c.271C>T	p.His91Tyr	missense_variant	3/20	1
SIN3B	ENST00000596802.5	c.271C>T	p.His91Tyr	missense_variant	3/8	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Oct 05, 2023

The c.271C>T (p.H91Y) alteration is located in exon 3 (coding exon 3) of the SIN3B gene. This alteration results from a C to T substitution at nucleotide position 271, causing the histidine (H) at amino acid position 91 to be replaced by a tyrosine (Y). 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	0.15
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
Cadd	Pathogenic	26
Dann	Uncertain	1.0
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.34	T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.3	L;L;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-2.5	D;.;D
REVEL	Benign	0.16
Sift	Uncertain	0.0040	D;.;D
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		0.99	D;D;P
Vest4		0.47
MutPred		0.45		Gain of phosphorylation at H91 (P = 0.0764);Gain of phosphorylation at H91 (P = 0.0764);Gain of phosphorylation at H91 (P = 0.0764);
MVP		0.21
MPC		1.5
ClinPred		0.92	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.45
gMVP		0.64

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-16942348;