12-57099997-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003153.5(STAT6):ā€‹c.1606C>Gā€‹(p.Arg536Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

STAT6
NM_003153.5 missense, splice_region

Scores

3
16
Splicing: ADA: 0.00003039
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.685
Variant links:
Genes affected
STAT6 (HGNC:11368): (signal transducer and activator of transcription 6) The protein encoded by this gene is a member of the STAT family of transcription factors. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. This protein plays a central role in exerting IL4 mediated biological responses. It is found to induce the expression of BCL2L1/BCL-X(L), which is responsible for the anti-apoptotic activity of IL4. Knockout studies in mice suggested the roles of this gene in differentiation of T helper 2 (Th2) cells, expression of cell surface markers, and class switch of immunoglobulins. Alternative splicing results in multiple transcript variants.[provided by RefSeq, May 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.15453056).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
STAT6NM_003153.5 linkuse as main transcriptc.1606C>G p.Arg536Gly missense_variant, splice_region_variant 14/22 ENST00000300134.8 NP_003144.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
STAT6ENST00000300134.8 linkuse as main transcriptc.1606C>G p.Arg536Gly missense_variant, splice_region_variant 14/221 NM_003153.5 ENSP00000300134 P1P42226-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461324
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
726924
show subpopulations
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:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGeneDxDec 07, 2023Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
-0.040
CADD
Benign
20
DANN
Benign
0.70
DEOGEN2
Benign
0.24
T;.;T;T;.;T;.;T
Eigen
Benign
-0.85
Eigen_PC
Benign
-0.62
FATHMM_MKL
Benign
0.69
D
LIST_S2
Benign
0.83
.;.;.;.;T;T;.;.
M_CAP
Benign
0.059
D
MetaRNN
Benign
0.15
T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.40
T
MutationAssessor
Benign
-0.94
N;.;N;N;.;N;.;.
MutationTaster
Benign
0.98
D;D;D;D;D;D;D
PrimateAI
Benign
0.48
T
PROVEAN
Benign
2.9
N;N;N;N;N;N;.;N
REVEL
Uncertain
0.49
Sift
Benign
1.0
T;T;T;T;T;T;.;T
Sift4G
Benign
0.56
T;T;T;T;T;T;.;.
Polyphen
0.13
B;.;B;B;.;B;.;.
Vest4
0.34
MutPred
0.66
Loss of MoRF binding (P = 0.0285);.;Loss of MoRF binding (P = 0.0285);Loss of MoRF binding (P = 0.0285);.;Loss of MoRF binding (P = 0.0285);Loss of MoRF binding (P = 0.0285);.;
MVP
0.62
MPC
0.59
ClinPred
0.23
T
GERP RS
1.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.49
gMVP
0.77

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000030
dbscSNV1_RF
Benign
0.034
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: chr12-57493780; API