3-18349525-C-T
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2
The NM_002971.6(SATB1):c.1937G>A(p.Arg646Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R646L) has been classified as Uncertain significance.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
SATB1
NM_002971.6 missense
NM_002971.6 missense
Scores
4
11
4
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 5.55
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 Likely_benign. Variant got -3 ACMG points.
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.
BS2
High AC in GnomAdExome4 at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SATB1 | NM_002971.6 | c.1937G>A | p.Arg646Gln | missense_variant | 11/11 | ENST00000338745.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SATB1 | ENST00000338745.11 | c.1937G>A | p.Arg646Gln | missense_variant | 11/11 | 1 | NM_002971.6 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251180Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135810
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GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461864Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727230
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GnomAD4 genome Cov.: 32
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
T;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;D;D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
T;T;T
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
M;.;M
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Uncertain
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
D;D;D
Vest4
MutPred
Loss of MoRF binding (P = 0.0373);.;Loss of MoRF binding (P = 0.0373);
MVP
MPC
1.5
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at