7-100181901-CAAAAAAAAA-CAAAAAAAAAA

Variant names:

• chr7-100181901-C-CA
• rs3041317
• NM_001282717.2:c.117-171dupA

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_001282717.2(STAG3):​c.117-171dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00583 in 70,100 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0058 (1 hom., cov: 25)
• Consequence: STAG3 NM_001282717.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.471

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00583 (409/70100) while in subpopulation AFR AF= 0.0163 (246/15086). AF 95% confidence interval is 0.0146. There are 1 homozygotes in gnomad4. There are 193 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAG3	NM_001282717.2	c.117-171dupA		intron_variant	Intron 2 of 33	ENST00000615138.5	NP_001269646.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAG3	ENST00000615138.5	c.117-189_117-188insA		intron_variant	Intron 2 of 33	1	NM_001282717.2	ENSP00000477973.1

Frequencies

GnomAD3 genomes AF: 0.00578 AC: 405 AN: 70122 Hom.: 1 Cov.: 25

Gnomad AFR AF: 0.0161

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00378

Gnomad ASJ AF: 0.00301

Gnomad EAS AF: 0.00575

Gnomad SAS AF: 0.00200

Gnomad FIN AF: 0.00239

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00284

Gnomad OTH AF: 0.00211

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

GnomAD4 genome AF: 0.00583 AC: 409 AN: 70100 Hom.: 1 Cov.: 25 AF XY: 0.00593 AC XY: 193 AN XY: 32540

Gnomad4 AFR AF: 0.0163

Gnomad4 AMR AF: 0.00378

Gnomad4 ASJ AF: 0.00301

Gnomad4 EAS AF: 0.00577

Gnomad4 SAS AF: 0.00250

Gnomad4 FIN AF: 0.00239

Gnomad4 NFE AF: 0.00284

Gnomad4 OTH AF: 0.00210

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs3041317; hg19: chr7-99779524;