3-18358711-A-G

Variant names:

• chr3-18358711-A-G
• rs7635386
• NM_002971.6:c.1576-6516T>C

Variant summary

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

The NM_002971.6(SATB1):​c.1576-6516T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 151,788 control chromosomes in the GnomAD database, including 7,939 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 0.30 (7939 hom., cov: 32)
• Consequence: SATB1 NM_002971.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.837
• Publications: 5 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SATB1	NM_002971.6	c.1576-6516T>C		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.1576-6516T>C		intron_variant	Intron 9 of 10	1	NM_002971.6	ENSP00000341024.5

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45584 AN: 151670 Hom.: 7938 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.300 AC: 45592 AN: 151788 Hom.: 7939 Cov.: 32 AF XY: 0.302 AC XY: 22438 AN XY: 74188

African (AFR) AF: 0.141 AC: 5866 AN: 41480

American (AMR) AF: 0.238 AC: 3626 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 846 AN: 3468

East Asian (EAS) AF: 0.380 AC: 1959 AN: 5158

South Asian (SAS) AF: 0.220 AC: 1060 AN: 4818

European-Finnish (FIN) AF: 0.506 AC: 5329 AN: 10542

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.381 AC: 25805 AN: 67792

Other (OTH) AF: 0.286 AC: 602 AN: 2104

Alfa AF: 0.346 Hom.: 36420

Bravo AF: 0.277

Asia WGS AF: 0.267 AC: 929 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.3
DANN	Benign	0.77
PhyloP100		0.84
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: rs7635386; hg19: chr3-18400203;