chr3-18349268-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_002971.6(SATB1):​c.2194G>T​(p.Val732Phe) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SATB1
NM_002971.6 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.67
Variant links:
Genes affected
SATB1 (HGNC:10541): (SATB homeobox 1) This gene encodes a matrix protein which binds nuclear matrix and scaffold-associating DNAs through a unique nuclear architecture. The protein recruits chromatin-remodeling factors in order to regulate chromatin structure and gene expression. [provided by RefSeq, Apr 2016]
TBC1D5 (HGNC:19166): (TBC1 domain family member 5) Enables AP-2 adaptor complex binding activity and retromer complex binding activity. Involved in several processes, including macroautophagy; positive regulation of receptor internalization; and retrograde transport, endosome to Golgi. Located in Golgi apparatus; autophagosome; and endosome membrane. Part of retromer complex. Colocalizes with AP-2 adaptor complex and Atg1/ULK1 kinase complex. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 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), SATB1. . Gene score misZ 3.9832 (greater than the threshold 3.09). Trascript score misZ 4.7333 (greater than threshold 3.09). GenCC has associacion of gene with syndromic intellectual disability, developmental delay with dysmorphic facies and dental anomalies.
BP4
Computational evidence support a benign effect (MetaRNN=0.10977411).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SATB1NM_002971.6 linkuse as main transcriptc.2194G>T p.Val732Phe missense_variant 11/11 ENST00000338745.11 NP_002962.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SATB1ENST00000338745.11 linkuse as main transcriptc.2194G>T p.Val732Phe missense_variant 11/111 NM_002971.6 ENSP00000341024 P1Q01826-1

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

Autism spectrum disorder Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingDepartment of Genetics, Rouen University Hospital, Normandy Center for Genomic and Personalized MedicineFeb 17, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.091
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
20
DANN
Benign
0.96
DEOGEN2
Benign
0.12
T;.;T
Eigen
Benign
-0.16
Eigen_PC
Benign
-0.049
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.87
.;D;D
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.11
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.34
N;.;N
MutationTaster
Benign
0.88
D;D;D
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-0.62
N;N;N
REVEL
Benign
0.064
Sift
Benign
0.054
T;D;T
Sift4G
Uncertain
0.055
T;T;T
Polyphen
0.010
B;P;B
Vest4
0.15
MutPred
0.23
Gain of loop (P = 0.002);.;Gain of loop (P = 0.002);
MVP
0.22
MPC
1.6
ClinPred
0.51
D
GERP RS
5.6
Varity_R
0.14
gMVP
0.54

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: chr3-18390760; API