rs772415685

Variant names:

• chr3-18349633-G-A
• rs772415685
• NM_002971.6:c.1829C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-18349633-G-A
• chr3-18349633-G-C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_002971.6(SATB1):​c.1829C>T​(p.Pro610Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,612,526 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: SATB1 NM_002971.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.71
• Publications: 0 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06688842).
• BS2: High AC in GnomAdExome4 at 14 AD gene.

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.1829C>T	p.Pro610Leu	missense	Exon 11 of 11	NP_002962.1	Q01826-1
	SATB1	NM_001195470.3		c.1925C>T	p.Pro642Leu	missense	Exon 12 of 12	NP_001182399.1	Q01826-2
	SATB1	NM_001322871.2		c.1925C>T	p.Pro642Leu	missense	Exon 12 of 12	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.1829C>T	p.Pro610Leu	missense	Exon 11 of 11	ENSP00000341024.5	Q01826-1
	SATB1	ENST00000417717.6	TSL:1	c.1925C>T	p.Pro642Leu	missense	Exon 12 of 12	ENSP00000399518.1	Q01826-2
	SATB1	ENST00000454909.6	TSL:1	c.1829C>T	p.Pro610Leu	missense	Exon 11 of 11	ENSP00000399708.2	Q01826-1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152082 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000205 AC: 5 AN: 244328 AF XY: 0.0000225

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000583

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000274

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000959 AC: 14 AN: 1460444 Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10 AN XY: 726514

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.0000448 AC: 2 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53042

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5330

European-Non Finnish (NFE) AF: 0.00000900 AC: 10 AN: 1111720

Other (OTH) AF: 0.0000332 AC: 2 AN: 60240

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152082 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74290

African (AFR) AF: 0.00 AC: 0 AN: 41424

American (AMR) AF: 0.00 AC: 0 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000248 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	13
DANN	Benign	0.83
DEOGEN2	Benign	0.10	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.7
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.045
Sift	Benign	0.87	T
Sift4G	Benign	0.12	T
Polyphen		0.0020	B
Vest4		0.30
MutPred		0.35		Loss of glycosylation at P610 (P = 5e-04)
MVP		0.35
MPC		1.0
ClinPred		0.023	T
GERP RS		2.0
Varity_R		0.028
gMVP		0.26
Mutation Taster		=95/5	polymorphism

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: rs772415685; hg19: chr3-18391125;