NM_005862.3:c.-83-41372T>C

Variant names:

• chr3-136672353-A-G
• rs3856637
• NM_005862.3:c.-83-41372T>C

Variant summary

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

The NM_005862.3(STAG1):​c.-83-41372T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 152,230 control chromosomes in the GnomAD database, including 6,361 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 0.29 (6361 hom., cov: 32)
• Consequence: STAG1 NM_005862.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01
• Publications: 2 publications found

Genes affected

STAG1 (HGNC:11354): (STAG1 cohesin complex component) This gene is a member of the SCC3 family and is expressed in the nucleus. It encodes a component of cohesin, a multisubunit protein complex that provides sister chromatid cohesion along the length of a chromosome from DNA replication through prophase and prometaphase, after which it is dissociated in preparation for segregation during anaphase. [provided by RefSeq, Jul 2008]

STAG1 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• intellectual disability, autosomal dominant 47

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

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 (AFR) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005862.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAG1	NM_005862.3	MANE Select	c.-83-41372T>C		intron	N/A	NP_005853.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAG1	ENST00000383202.7	TSL:1 MANE Select	c.-83-41372T>C		intron	N/A	ENSP00000372689.2
	STAG1	ENST00000236698.9	TSL:1	c.-83-41372T>C		intron	N/A	ENSP00000236698.5
	STAG1	ENST00000483235.5	TSL:1	n.-83-41372T>C		intron	N/A	ENSP00000419093.1

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43773 AN: 152112 Hom.: 6355 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.288 AC: 43801 AN: 152230 Hom.: 6361 Cov.: 32 AF XY: 0.287 AC XY: 21330 AN XY: 74442

African (AFR) AF: 0.319 AC: 13252 AN: 41522

American (AMR) AF: 0.263 AC: 4020 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 1250 AN: 3472

East Asian (EAS) AF: 0.136 AC: 705 AN: 5180

South Asian (SAS) AF: 0.199 AC: 960 AN: 4830

European-Finnish (FIN) AF: 0.278 AC: 2950 AN: 10604

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.287 AC: 19550 AN: 68006

Other (OTH) AF: 0.304 AC: 644 AN: 2116

Alfa AF: 0.267 Hom.: 3169

Bravo AF: 0.289

Asia WGS AF: 0.177 AC: 618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.1
DANN	Benign	0.73
PhyloP100		2.0
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: rs3856637; hg19: chr3-136391195;