7-100182659-C-T

Variant names:

• chr7-100182659-C-T
• rs4729579
• NM_001282717.2:c.220-64C>T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2 BP4_Strong BS1

The NM_001282717.2(STAG3):​c.220-64C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00144 in 1,564,640 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0015 (1 hom.)
• Consequence: STAG3 NM_001282717.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0520

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 -6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00114 (174/152008) while in subpopulation NFE AF= 0.00193 (131/67962). AF 95% confidence interval is 0.00166. There are 0 homozygotes in gnomad4. There are 74 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAG3	NM_001282717.2	c.220-64C>T		intron_variant	Intron 3 of 33	ENST00000615138.5	NP_001269646.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAG3	ENST00000615138.5	c.220-64C>T		intron_variant	Intron 3 of 33	1	NM_001282717.2	ENSP00000477973.1

Frequencies

GnomAD3 genomes AF: 0.00115 AC: 175 AN: 151890 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000774

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000569

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00193

Gnomad OTH AF: 0.000479

GnomAD4 exome AF: 0.00147 AC: 2072 AN: 1412632 Hom.: 1 AF XY: 0.00145 AC XY: 1024 AN XY: 705480

Gnomad4 AFR exome AF: 0.000625

Gnomad4 AMR exome AF: 0.000231

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.0000356

Gnomad4 FIN exome AF: 0.00107

Gnomad4 NFE exome AF: 0.00180

Gnomad4 OTH exome AF: 0.000802

GnomAD4 genome AF: 0.00114 AC: 174 AN: 152008 Hom.: 0 Cov.: 31 AF XY: 0.000996 AC XY: 74 AN XY: 74312

Gnomad4 AFR AF: 0.000772

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000569

Gnomad4 NFE AF: 0.00193

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.00115 Hom.: 238

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.1
DANN	Benign	0.46

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: rs4729579; hg19: chr7-99780282; COSMIC: COSV57932110; COSMIC: COSV57932110;