NM_002971.6:c.1576-4162G>A

Variant names:

• chr3-18356357-C-T
• rs6577641
• NM_002971.6:c.1576-4162G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002971.6(SATB1):​c.1576-4162G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.703 in 148,746 control chromosomes in the GnomAD database, including 37,488 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 0.70 (37488 hom., cov: 25)
• Consequence: SATB1 NM_002971.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.204
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.893 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SATB1	NM_002971.6	MANE Select	c.1576-4162G>A		intron	N/A	NP_002962.1	Q01826-1
	SATB1	NM_001195470.3		c.1576-4162G>A		intron	N/A	NP_001182399.1	Q01826-2
	SATB1	NM_001322871.2		c.1576-4162G>A		intron	N/A	NP_001309800.1	Q01826-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SATB1	ENST00000338745.11	TSL:1 MANE Select	c.1576-4162G>A		intron	N/A	ENSP00000341024.5	Q01826-1
	SATB1	ENST00000417717.6	TSL:1	c.1576-4162G>A		intron	N/A	ENSP00000399518.1	Q01826-2
	SATB1	ENST00000454909.6	TSL:1	c.1576-4162G>A		intron	N/A	ENSP00000399708.2	Q01826-1

Frequencies

GnomAD3 genomes AF: 0.702 AC: 104395 AN: 148634 Hom.: 37439 Cov.: 25

Gnomad AFR AF: 0.836

Gnomad AMI AF: 0.683

Gnomad AMR AF: 0.726

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.915

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.710

Gnomad MID AF: 0.470

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.649

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

GnomAD4 genome AF: 0.703 AC: 104505 AN: 148746 Hom.: 37488 Cov.: 25 AF XY: 0.708 AC XY: 51245 AN XY: 72348

African (AFR) AF: 0.836 AC: 33962 AN: 40618

American (AMR) AF: 0.726 AC: 10829 AN: 14914

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1613 AN: 3428

East Asian (EAS) AF: 0.915 AC: 4654 AN: 5088

South Asian (SAS) AF: 0.667 AC: 3145 AN: 4714

European-Finnish (FIN) AF: 0.710 AC: 7027 AN: 9892

Middle Eastern (MID) AF: 0.467 AC: 129 AN: 276

European-Non Finnish (NFE) AF: 0.616 AC: 41185 AN: 66854

Other (OTH) AF: 0.653 AC: 1345 AN: 2060

Alfa AF: 0.632 Hom.: 51402

Bravo AF: 0.710

Asia WGS AF: 0.805 AC: 2788 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.6
DANN	Benign	0.67
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6577641; hg19: chr3-18397849;