Genetic Variant SATB1:p.Arg646Leu (chr3-18349525-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002971.6(SATB1):c.1937G>T(p.Arg646Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. R646Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

SATB1
NM_002971.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.55

Publications

0 publications found

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]

SATB1 links:

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]

TBC1D5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002971.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SATB1	NM_002971.6	MANE Select	c.1937G>T	p.Arg646Leu	missense	Exon 11 of 11	NP_002962.1	Q01826-1
SATB1	NM_001195470.3		c.2033G>T	p.Arg678Leu	missense	Exon 12 of 12	NP_001182399.1	Q01826-2
SATB1	NM_001322871.2		c.2033G>T	p.Arg678Leu	missense	Exon 12 of 12	NP_001309800.1	Q01826-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SATB1	ENST00000338745.11	TSL:1 MANE Select	c.1937G>T	p.Arg646Leu	missense	Exon 11 of 11	ENSP00000341024.5	Q01826-1
SATB1	ENST00000417717.6	TSL:1	c.2033G>T	p.Arg678Leu	missense	Exon 12 of 12	ENSP00000399518.1	Q01826-2
SATB1	ENST00000454909.6	TSL:1	c.1937G>T	p.Arg646Leu	missense	Exon 11 of 11	ENSP00000399708.2	Q01826-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

SATB1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.60

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.10

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.73

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

M_CAP

Pathogenic

0.57

MetaRNN

Uncertain

0.66

MetaSVM

Pathogenic

1.1

MutationAssessor

Uncertain

2.5

PhyloP100

5.6

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-3.2

REVEL

Pathogenic

0.72

Sift

Uncertain

0.0020

Sift4G

Benign

0.16

Polyphen

0.98

Vest4

0.35

MutPred

0.60

Loss of MoRF binding (P = 0.0315)

MVP

0.78

MPC

1.9

ClinPred

0.98

GERP RS

5.1

Varity_R

0.47

gMVP

0.89

Mutation Taster

=33/67

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over