Variant chr15-75372148-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 3P and 3B. PM2PP2BP4_ModerateBP6

The NM_001145358.2(SIN3A):c.3653C>G(p.Thr1218Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

SIN3A
NM_001145358.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.90

Variant links:

Genes affected

SIN3A (HGNC:19353): (SIN3 transcription regulator family member A) The protein encoded by this gene is a transcriptional regulatory protein. It contains paired amphipathic helix (PAH) domains, which are important for protein-protein interactions and may mediate repression by the Mad-Max complex. [provided by RefSeq, Jul 2008]

SIN3A links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), SIN3A. . Gene score misZ 4.3926 (greater than the threshold 3.09). Trascript score misZ 5.1543 (greater than threshold 3.09). GenCC has associacion of gene with chromosome 15q24 deletion syndrome, SIN3A-related intellectual disability syndrome due to a point mutation, congenital diaphragmatic hernia, SIN3A-related intellectual disability syndrome, autism, susceptibility to, 15.

BP4

Computational evidence support a benign effect (MetaRNN=0.11290732).

BP6

Variant 15-75372148-G-C is Benign according to our data. Variant chr15-75372148-G-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2435950.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIN3A	NM_001145358.2 linkuse as main transcript	c.3653C>G	p.Thr1218Ser	missense_variant	21/21	ENST00000394947.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIN3A	ENST00000394947.8 linkuse as main transcript	c.3653C>G	p.Thr1218Ser	missense_variant	21/21	1	NM_001145358.2	P4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

SIN3A-related intellectual disability syndrome due to a point mutation

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Revvity Omics, Revvity

Mar 24, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.24

T;T;T

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.22

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.81

.;.;T

M_CAP

Benign

0.0049

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

N;N;N

MutationTaster

Benign

0.59

D;D;D

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.11

N;N;N

REVEL

Benign

0.042

Sift

Benign

0.77

T;T;T

Sift4G

Benign

0.31

T;T;T

Polyphen

0.0010

B;B;B

Vest4

0.099

MutPred

0.39

Loss of phosphorylation at T1218 (P = 0.0347);Loss of phosphorylation at T1218 (P = 0.0347);Loss of phosphorylation at T1218 (P = 0.0347);

MVP

0.46

MPC

0.58

ClinPred

0.38

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.028

gMVP

0.63

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over