chr7-100182751-G-C

Variant names:

• chr7-100182751-G-C
• NM_001282717.2:c.248G>C

Variant summary

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

The NM_001282717.2(STAG3):​c.248G>C​(p.Arg83Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: STAG3 NM_001282717.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.45

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=0.09568134).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAG3	NM_001282717.2	c.248G>C	p.Arg83Pro	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.248G>C	p.Arg83Pro	missense_variant	Exon 4 of 34	1	NM_001282717.2	ENSP00000477973.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461748 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 727170

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: 0.00000540

Gnomad4 OTH exome AF: 0.00

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

Nov 13, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.248G>C (p.R83P) alteration is located in exon 4 (coding exon 3) of the STAG3 gene. This alteration results from a G to C substitution at nucleotide position 248, causing the arginine (R) at amino acid position 83 to be replaced by a proline (P). 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	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.019
DANN	Benign	0.82
DEOGEN2	Benign	0.079	T;.;.;T;.;T;T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.74	.;.;T;T;T;T;T;T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.096	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;L;L;.;.;L;.;.
PrimateAI	Benign	0.18	T
PROVEAN	Benign	-1.7	N;N;.;.;N;N;D;N
REVEL	Benign	0.086
Sift	Benign	0.041	D;D;.;.;D;D;D;D
Sift4G	Benign	0.14	T;T;T;T;D;T;D;D
Polyphen		0.0090	B;.;.;.;.;B;.;.
Vest4		0.31
MutPred		0.31		Loss of MoRF binding (P = 0.0321);Loss of MoRF binding (P = 0.0321);Loss of MoRF binding (P = 0.0321);Loss of MoRF binding (P = 0.0321);Loss of MoRF binding (P = 0.0321);Loss of MoRF binding (P = 0.0321);Loss of MoRF binding (P = 0.0321);Loss of MoRF binding (P = 0.0321);
MVP		0.19
MPC		0.86
ClinPred		0.34	T
GERP RS		-11
Varity_R		0.17
gMVP		0.28

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: chr7-99780374;