Genetic Variant STAG3:c.116+222_116+225dupTTTT (chr7-100180880-G-GTTTT) – 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+222_116+225dupTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000473 in 221,764 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 0.0000073 ( 0 hom., cov: 27)

Exomes 𝑓: 0.0012 ( 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+222_116+225dupTTTT	intron	N/A	NP_001269646.1	D6W5U7
STAG3	NM_001375438.1		c.116+222_116+225dupTTTT	intron	N/A	NP_001362367.1	D6W5U7
STAG3	NM_001282716.1		c.116+222_116+225dupTTTT	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+197_116+198insTTTT	intron	N/A	ENSP00000477973.1	D6W5U7
STAG3	ENST00000317296.9	TSL:1	c.116+197_116+198insTTTT	intron	N/A	ENSP00000319318.5	Q9UJ98-1
STAG3	ENST00000426455.5	TSL:1	c.116+197_116+198insTTTT	intron	N/A	ENSP00000400359.1	Q9UJ98-1

Frequencies

GnomAD3 genomes

AF:

0.00000731

AC:

AN:

136842

Hom.:

Cov.:

show subpopulations

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:

0.000134

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00122

AC:

104

AN:

84922

Hom.:

Cov.:

AF XY:

0.00143

AC XY:

AN XY:

46218

show subpopulations

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

African (AFR)

AF:

0.00102

AC:

AN:

1960

American (AMR)

AF:

0.00128

AC:

AN:

3126

Ashkenazi Jewish (ASJ)

AF:

0.00189

AC:

AN:

2116

East Asian (EAS)

AF:

0.000611

AC:

AN:

4912

South Asian (SAS)

AF:

0.00113

AC:

AN:

11476

European-Finnish (FIN)

AF:

0.00154

AC:

AN:

5206

Middle Eastern (MID)

AF:

0.00362

AC:

AN:

276

European-Non Finnish (NFE)

AF:

0.00106

AC:

AN:

50872

Other (OTH)

AF:

0.00301

AC:

AN:

4978

⚠️ 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: 0.260

Heterozygous variant carriers

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:

0.00000731

AC:

AN:

136842

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

65576

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

37392

American (AMR)

AF:

0.00

AC:

AN:

13450

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3286

East Asian (EAS)

AF:

0.00

AC:

AN:

4750

South Asian (SAS)

AF:

0.00

AC:

AN:

4300

European-Finnish (FIN)

AF:

0.000134

AC:

AN:

7490

Middle Eastern (MID)

AF:

0.00

AC:

AN:

274

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

63188

Other (OTH)

AF:

0.00

AC:

AN:

1844

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 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: 0.275

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

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-GTTTTTTTTT

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