chr15-75372181-T-C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2

The NM_001145358.2(SIN3A):ā€‹c.3620A>Gā€‹(p.His1207Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,611,720 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000048 ( 0 hom. )

Consequence

SIN3A
NM_001145358.2 missense

Scores

2
12
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.94
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 Likely_benign. Variant got -3 ACMG points.

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.
BS2
High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SIN3ANM_001145358.2 linkuse as main transcriptc.3620A>G p.His1207Arg missense_variant 21/21 ENST00000394947.8 NP_001138830.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SIN3AENST00000394947.8 linkuse as main transcriptc.3620A>G p.His1207Arg missense_variant 21/211 NM_001145358.2 ENSP00000378402 P4

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
152044
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000480
AC:
7
AN:
1459676
Hom.:
0
Cov.:
31
AF XY:
0.00000551
AC XY:
4
AN XY:
725798
show subpopulations
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:
0.00000630
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
152044
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74258
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000312
Hom.:
0
Bravo
AF:
0.00000378

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 submitterclinical testingRevvity Omics, RevvityMar 19, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.84
BayesDel_addAF
Uncertain
0.096
D
BayesDel_noAF
Benign
-0.10
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.74
D;D;D
Eigen
Uncertain
0.21
Eigen_PC
Uncertain
0.32
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.90
.;.;D
M_CAP
Benign
0.028
D
MetaRNN
Uncertain
0.67
D;D;D
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.7
M;M;M
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.77
T
PROVEAN
Uncertain
-4.1
D;D;D
REVEL
Uncertain
0.35
Sift
Benign
0.056
T;T;T
Sift4G
Uncertain
0.056
T;T;T
Polyphen
0.38
B;B;B
Vest4
0.77
MutPred
0.33
Gain of disorder (P = 0.1592);Gain of disorder (P = 0.1592);Gain of disorder (P = 0.1592);
MVP
0.68
MPC
0.90
ClinPred
0.97
D
GERP RS
5.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.52
gMVP
0.88

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.

Other links and lift over

dbSNP: rs2072763773; hg19: chr15-75664522; API