7-100182145-C-T

Variant names:

• chr7-100182145-C-T
• rs200232685
• NM_001282717.2:c.172C>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.172C>T​(p.Arg58Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,462 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.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: STAG3 NM_001282717.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.158

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=0.18240446).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAG3	NM_001282717.2	c.172C>T	p.Arg58Cys	missense_variant	Exon 3 of 34	ENST00000615138.5	NP_001269646.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAG3	ENST00000615138.5	c.172C>T	p.Arg58Cys	missense_variant	Exon 3 of 34	1	NM_001282717.2	ENSP00000477973.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251460 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135908

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1461462 Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 4 AN XY: 727058

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000108

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

Alfa AF: 0.0000277 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T;.;.;T;.;T;T;.
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.80	.;.;T;T;T;T;T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.18	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.6	M;M;M;.;.;M;.;.
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-2.3	N;N;.;.;D;N;D;N
REVEL	Benign	0.12
Sift	Pathogenic	0.0	D;D;.;.;D;D;D;D
Sift4G	Uncertain	0.0060	D;D;D;D;D;D;D;D
Polyphen		0.48	P;.;.;.;.;P;.;.
Vest4		0.14
MutPred		0.27		Loss of MoRF binding (P = 0.0175);Loss of MoRF binding (P = 0.0175);Loss of MoRF binding (P = 0.0175);Loss of MoRF binding (P = 0.0175);Loss of MoRF binding (P = 0.0175);Loss of MoRF binding (P = 0.0175);Loss of MoRF binding (P = 0.0175);Loss of MoRF binding (P = 0.0175);
MVP		0.59
MPC		1.2
ClinPred		0.91	D
GERP RS		4.6
Varity_R		0.13
gMVP		0.26

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: rs200232685; hg19: chr7-99779768;