rs9841621

Positions:

• chr3-18367585-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002971.6(SATB1):​c.1575+10585T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,100 control chromosomes in the GnomAD database, including 2,101 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (2101 hom., cov: 32)
• Consequence: SATB1 NM_002971.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SATB1	NM_002971.6	c.1575+10585T>C		intron_variant		ENST00000338745.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SATB1	ENST00000338745.11	c.1575+10585T>C		intron_variant		1	NM_002971.6	P1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17201 AN: 151980 Hom.: 2093 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0793

Gnomad ASJ AF: 0.0409

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.0262

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0208

Gnomad OTH AF: 0.0986

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.113 AC: 17243 AN: 152100 Hom.: 2101 Cov.: 32 AF XY: 0.116 AC XY: 8598 AN XY: 74384

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.0794

Gnomad4 ASJ AF: 0.0409

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.0262

Gnomad4 NFE AF: 0.0208

Gnomad4 OTH AF: 0.0971

Alfa AF: 0.0380 Hom.: 739

Bravo AF: 0.124

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.066
DANN	Benign	0.22

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: rs9841621; hg19: chr3-18409077;