chr7-100182834-A-T

Variant names:

• chr7-100182834-A-T
• NM_001282717.2:c.331A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001282717.2(STAG3):​c.331A>T​(p.Met111Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M111V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: STAG3 NM_001282717.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.75

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20779848).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAG3	NM_001282717.2	c.331A>T	p.Met111Leu	missense_variant	Exon 4 of 34	ENST00000615138.5	NP_001269646.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAG3	ENST00000615138.5	c.331A>T	p.Met111Leu	missense_variant	Exon 4 of 34	1	NM_001282717.2	ENSP00000477973.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461656 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727134

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	0.010	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.092	T;.;.;T;.;T;T;.
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.011
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.61	.;.;T;D;D;D;T;T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.21	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	2.9	M;M;M;.;.;M;.;.
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.2	N;N;.;.;N;N;D;N
REVEL	Benign	0.12
Sift	Benign	0.23	T;T;.;.;D;T;D;D
Sift4G	Benign	0.40	T;T;T;T;T;T;D;T
Polyphen		0.0020	B;.;.;.;.;B;.;.
Vest4		0.56
MutPred		0.37		Loss of ubiquitination at K108 (P = 0.0672);Loss of ubiquitination at K108 (P = 0.0672);Loss of ubiquitination at K108 (P = 0.0672);Loss of ubiquitination at K108 (P = 0.0672);Loss of ubiquitination at K108 (P = 0.0672);Loss of ubiquitination at K108 (P = 0.0672);Loss of ubiquitination at K108 (P = 0.0672);Loss of ubiquitination at K108 (P = 0.0672);
MVP		0.30
MPC		0.46
ClinPred		0.92	D
GERP RS		4.1
Varity_R		0.17
gMVP		0.32

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-99780457; COSMIC: COSV100425934; COSMIC: COSV100425934;