15-75372011-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001145358.2(SIN3A):​c.3790G>A​(p.Val1264Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SIN3A
NM_001145358.2 missense

Scores

4
9
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.86
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SIN3ANM_001145358.2 linkc.3790G>A p.Val1264Ile missense_variant Exon 21 of 21 ENST00000394947.8 NP_001138830.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SIN3AENST00000394947.8 linkc.3790G>A p.Val1264Ile missense_variant Exon 21 of 21 1 NM_001145358.2 ENSP00000378402.3 Q96ST3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Dec 01, 2024
CeGaT Center for Human Genetics Tuebingen
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

SIN3A: PM2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.45
BayesDel_addAF
Uncertain
0.013
T
BayesDel_noAF
Benign
-0.22
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.50
T;T;T
Eigen
Pathogenic
0.77
Eigen_PC
Pathogenic
0.74
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.95
.;.;D
M_CAP
Benign
0.046
D
MetaRNN
Uncertain
0.56
D;D;D
MetaSVM
Benign
-0.37
T
MutationAssessor
Uncertain
2.7
M;M;M
PrimateAI
Pathogenic
0.80
T
PROVEAN
Benign
-0.69
N;N;N
REVEL
Benign
0.25
Sift
Uncertain
0.0040
D;D;D
Sift4G
Uncertain
0.0090
D;D;D
Polyphen
0.99
D;D;D
Vest4
0.51
MutPred
0.47
Gain of catalytic residue at V1264 (P = 0.0337);Gain of catalytic residue at V1264 (P = 0.0337);Gain of catalytic residue at V1264 (P = 0.0337);
MVP
0.59
MPC
1.1
ClinPred
0.91
D
GERP RS
5.1
Varity_R
0.26
gMVP
0.81

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: chr15-75664352; API