chr7-100183032-T-C

Variant names:

• chr7-100183032-T-C
• rs10252884
• NM_001282717.2:c.336+193T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001282717.2(STAG3):​c.336+193T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 151,716 control chromosomes in the GnomAD database, including 5,817 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.25 (5817 hom., cov: 31)
• Consequence: STAG3 NM_001282717.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.03
• Publications: 3 publications found

Genes affected

STAG3 (HGNC:11356): (STAG3 cohesin complex component) The protein encoded by this gene is expressed in the nucleus and is a subunit of the cohesin complex which regulates the cohesion of sister chromatids during cell division. A mutation in this gene is associated with premature ovarian failure. Alternate splicing results in multiple transcript variants encoding distinct isoforms. This gene has multiple pseudogenes. [provided by RefSeq, Apr 2014]

STAG3 Gene-Disease associations (from GenCC):

• premature ovarian failure 8

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• spermatogenic failure 61

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 7-100183032-T-C is Benign according to our data. Variant chr7-100183032-T-C is described in ClinVar as Benign. ClinVar VariationId is 1272177.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282717.2. 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
	STAG3	NM_001282717.2	MANE Select	c.336+193T>C		intron	N/A	NP_001269646.1	D6W5U7
	STAG3	NM_001375438.1		c.336+193T>C		intron	N/A	NP_001362367.1	D6W5U7
	STAG3	NM_001282716.1		c.336+193T>C		intron	N/A	NP_001269645.1	Q9UJ98-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAG3	ENST00000615138.5	TSL:1 MANE Select	c.336+193T>C		intron	N/A	ENSP00000477973.1	D6W5U7
	STAG3	ENST00000317296.9	TSL:1	c.336+193T>C		intron	N/A	ENSP00000319318.5	Q9UJ98-1
	STAG3	ENST00000426455.5	TSL:1	c.336+193T>C		intron	N/A	ENSP00000400359.1	Q9UJ98-1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37413 AN: 151600 Hom.: 5800 Cov.: 31

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.247 AC: 37443 AN: 151716 Hom.: 5817 Cov.: 31 AF XY: 0.253 AC XY: 18771 AN XY: 74148

African (AFR) AF: 0.110 AC: 4538 AN: 41442

American (AMR) AF: 0.424 AC: 6439 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 637 AN: 3472

East Asian (EAS) AF: 0.623 AC: 3194 AN: 5128

South Asian (SAS) AF: 0.269 AC: 1293 AN: 4806

European-Finnish (FIN) AF: 0.274 AC: 2878 AN: 10502

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17675 AN: 67864

Other (OTH) AF: 0.241 AC: 507 AN: 2102

Alfa AF: 0.117 Hom.: 211

Bravo AF: 0.255

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.34
PhyloP100		1.0
Mutation Taster		=19/81	disease causing (long InDel)

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: rs10252884; hg19: chr7-99780655; COSMIC: COSV57932349; COSMIC: COSV57932349;