3-18356357-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SATB1	NM_002971.6	c.1576-4162G>A		intron_variant	Intron 9 of 10	ENST00000338745.11	NP_002962.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SATB1	ENST00000338745.11	c.1576-4162G>A		intron_variant	Intron 9 of 10	1	NM_002971.6	ENSP00000341024.5

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

Gnomad4 AFR AF: 0.836

Gnomad4 AMR AF: 0.726

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.915

Gnomad4 SAS AF: 0.667

Gnomad4 FIN AF: 0.710

Gnomad4 NFE AF: 0.616

Gnomad4 OTH AF: 0.653

Alfa AF: 0.623 Hom.: 39665

Bravo AF: 0.710

Asia WGS AF: 0.805 AC: 2788 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.6
DANN	Benign	0.67

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: rs6577641; hg19: chr3-18397849;