3-136341462-C-T
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP2BP4_ModerateBP6BS2
The ENST00000383202.7(STAG1):c.3536G>A(p.Arg1179Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
STAG1
ENST00000383202.7 missense
ENST00000383202.7 missense
Scores
3
4
12
Clinical Significance
Conservation
PhyloP100: 7.50
Genes affected
STAG1 (HGNC:11354): (STAG1 cohesin complex component) This gene is a member of the SCC3 family and is expressed in the nucleus. It encodes a component of cohesin, a multisubunit protein complex that provides sister chromatid cohesion along the length of a chromosome from DNA replication through prophase and prometaphase, after which it is dissociated in preparation for segregation during anaphase. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), STAG1. . Gene score misZ 4.4429 (greater than the threshold 3.09). Trascript score misZ 4.1606 (greater than threshold 3.09). GenCC has associacion of gene with complex neurodevelopmental disorder, intellectual disability, autosomal dominant 47.
BP4
Computational evidence support a benign effect (MetaRNN=0.24322504).
BP6
Variant 3-136341462-C-T is Benign according to our data. Variant chr3-136341462-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2727290.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
BS2
High AC in GnomAdExome4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
STAG1 | NM_005862.3 | c.3536G>A | p.Arg1179Lys | missense_variant | 31/34 | ENST00000383202.7 | NP_005853.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
STAG1 | ENST00000383202.7 | c.3536G>A | p.Arg1179Lys | missense_variant | 31/34 | 1 | NM_005862.3 | ENSP00000372689 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152234Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251174Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135750
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GnomAD4 exome AF: 0.00000342 AC: 5AN: 1460786Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1AN XY: 726790
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152234Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74378
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 13, 2023 | The c.3536G>A (p.R1179K) alteration is located in exon 31 (coding exon 30) of the STAG1 gene. This alteration results from a G to A substitution at nucleotide position 3536, causing the arginine (R) at amino acid position 1179 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 03, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Benign
T;T
Polyphen
D;.
Vest4
MutPred
Gain of methylation at R1179 (P = 0.0261);.;
MVP
MPC
ClinPred
T
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at