chr7-100180615-C-T

Position:

• chr7-100180615-C-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.59C>T​(p.Ser20Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: STAG3 NM_001282717.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.63

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=0.15099353).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAG3	NM_001282717.2	c.59C>T	p.Ser20Phe	missense_variant	2/34	ENST00000615138.5	NP_001269646.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAG3	ENST00000615138.5	c.59C>T	p.Ser20Phe	missense_variant	2/34	1	NM_001282717.2	ENSP00000477973.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 24, 2023

The c.59C>T (p.S20F) alteration is located in exon 2 (coding exon 1) of the STAG3 gene. This alteration results from a C to T substitution at nucleotide position 59, causing the serine (S) at amino acid position 20 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.070	T;.;.;T;.;T;T;.
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.80	.;.;T;T;T;T;T;T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.15	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.6	M;M;M;.;.;M;.;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.64	N;N;.;.;N;N;D;N
REVEL	Benign	0.10
Sift	Uncertain	0.0050	D;D;.;.;D;D;D;D
Sift4G	Uncertain	0.016	D;D;D;D;D;D;T;D
Polyphen		0.61	P;.;.;.;.;P;.;.
Vest4		0.21
MutPred		0.15		Loss of phosphorylation at S20 (P = 0.0047);Loss of phosphorylation at S20 (P = 0.0047);Loss of phosphorylation at S20 (P = 0.0047);Loss of phosphorylation at S20 (P = 0.0047);Loss of phosphorylation at S20 (P = 0.0047);Loss of phosphorylation at S20 (P = 0.0047);Loss of phosphorylation at S20 (P = 0.0047);Loss of phosphorylation at S20 (P = 0.0047);
MVP		0.68
MPC		0.96
ClinPred		0.55	D
GERP RS		4.6
Varity_R		0.12
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-99778238;