Genetic Variant STAG3:c.116+223_116+225dupTTT (chr7-100180880-G-GTTT) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001282717.2(STAG3):c.116+223_116+225dupTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00281 in 221,444 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000095 ( 0 hom., cov: 27)

Exomes 𝑓: 0.0072 ( 0 hom. )

Consequence

STAG3
NM_001282717.2 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0530

Publications

0 publications found

Variant links:

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)

STAG3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
STAG3	NM_001282717.2	MANE Select	c.116+223_116+225dupTTT	intron	N/A	NP_001269646.1	D6W5U7
STAG3	NM_001375438.1		c.116+223_116+225dupTTT	intron	N/A	NP_001362367.1	D6W5U7
STAG3	NM_001282716.1		c.116+223_116+225dupTTT	intron	N/A	NP_001269645.1	Q9UJ98-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
STAG3	ENST00000615138.5	TSL:1 MANE Select	c.116+201_116+202insTTT	intron	N/A	ENSP00000477973.1	D6W5U7
STAG3	ENST00000317296.9	TSL:1	c.116+201_116+202insTTT	intron	N/A	ENSP00000319318.5	Q9UJ98-1
STAG3	ENST00000426455.5	TSL:1	c.116+201_116+202insTTT	intron	N/A	ENSP00000400359.1	Q9UJ98-1

Frequencies

GnomAD3 genomes

AF:

0.0000950

AC:

AN:

136834

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000535

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000149

Gnomad ASJ

AF:

0.000304

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000534

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000475

Gnomad OTH

AF:

0.000542

GnomAD4 exome

AF:

0.00720

AC:

609

AN:

84608

Hom.:

Cov.:

AF XY:

0.00756

AC XY:

348

AN XY:

46020

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00411

AC:

AN:

1946

American (AMR)

AF:

0.00804

AC:

AN:

3108

Ashkenazi Jewish (ASJ)

AF:

0.00571

AC:

AN:

2102

East Asian (EAS)

AF:

0.00388

AC:

AN:

4902

South Asian (SAS)

AF:

0.00805

AC:

AN:

11432

European-Finnish (FIN)

AF:

0.00636

AC:

AN:

5192

Middle Eastern (MID)

AF:

0.00735

AC:

AN:

272

European-Non Finnish (NFE)

AF:

0.00771

AC:

391

AN:

50702

Other (OTH)

AF:

0.00545

AC:

AN:

4952

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.282

Heterozygous variant carriers

118

178

237

296

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000950

AC:

AN:

136836

Hom.:

Cov.:

AF XY:

0.0000915

AC XY:

AN XY:

65600

show subpopulations

African (AFR)

AF:

0.0000534

AC:

AN:

37438

American (AMR)

AF:

0.000149

AC:

AN:

13466

Ashkenazi Jewish (ASJ)

AF:

0.000304

AC:

AN:

3288

East Asian (EAS)

AF:

0.00

AC:

AN:

4732

South Asian (SAS)

AF:

0.00

AC:

AN:

4274

European-Finnish (FIN)

AF:

0.000534

AC:

AN:

7486

Middle Eastern (MID)

AF:

0.00

AC:

AN:

252

European-Non Finnish (NFE)

AF:

0.0000475

AC:

AN:

63176

Other (OTH)

AF:

0.000539

AC:

AN:

1856

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.410

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.053

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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7-100180880-GTTTTT-GTTTTTTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over