3-18349534-T-C

Position:

• chr3-18349534-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_002971.6(SATB1):​c.1928A>G​(p.Gln643Arg) 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. 14/21 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.93

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]

ACMG classification

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=0.08905545).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SATB1	NM_002971.6	c.1928A>G	p.Gln643Arg	missense_variant	11/11	ENST00000338745.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SATB1	ENST00000338745.11	c.1928A>G	p.Gln643Arg	missense_variant	11/11	1	NM_002971.6	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000312 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	15
DANN	Benign	0.90
DEOGEN2	Benign	0.12	T;.;T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.69	.;T;T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.089	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.90	L;.;L
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	0.81	N;N;N
REVEL	Benign	0.029
Sift	Benign	0.19	T;T;T
Sift4G	Benign	0.30	T;T;T
Polyphen		0.0080	B;B;B
Vest4		0.069
MutPred		0.19		Gain of MoRF binding (P = 0.0264);.;Gain of MoRF binding (P = 0.0264);
MVP		0.75
MPC		1.1
ClinPred		0.44	T
GERP RS		3.9
Varity_R		0.19
gMVP		0.68

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

Other links and lift over

dbSNP: rs1694237569; hg19: chr3-18391026;