chr7-100183032-T-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAG3	NM_001282717.2	c.336+193T>C		intron_variant	Intron 4 of 33	ENST00000615138.5	NP_001269646.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAG3	ENST00000615138.5	c.336+193T>C		intron_variant	Intron 4 of 33	1	NM_001282717.2	ENSP00000477973.1

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

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.424

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.623

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.241

Alfa AF: 0.117 Hom.: 211

Bravo AF: 0.255

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 16, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.34

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