12-57099375-C-T
Position:
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP3BP4_StrongBS2
The NM_003153.5(STAT6):c.1810G>A(p.Asp604Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000731 in 1,613,992 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000056 ( 0 hom. )
Consequence
STAT6
NM_003153.5 missense
NM_003153.5 missense
Scores
10
6
3
Clinical Significance
Conservation
PhyloP100: 5.86
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 Benign. Variant got -7 ACMG points.
PP3
Multiple lines of computational evidence support a deleterious effect 7: AlphaMissense, Cadd, Dann, Eigen, PrimateAI, PROVEAN, REVEL [when max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]
BP4
Computational evidence support a benign effect (MetaRNN=0.050684392).
BS2
High AC in GnomAd4 at 36 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
STAT6 | NM_003153.5 | c.1810G>A | p.Asp604Asn | missense_variant | 16/22 | ENST00000300134.8 | NP_003144.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
STAT6 | ENST00000300134.8 | c.1810G>A | p.Asp604Asn | missense_variant | 16/22 | 1 | NM_003153.5 | ENSP00000300134 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000237 AC: 36AN: 152118Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
36
AN:
152118
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000596 AC: 15AN: 251492Hom.: 0 AF XY: 0.0000736 AC XY: 10AN XY: 135920
GnomAD3 exomes
AF:
AC:
15
AN:
251492
Hom.:
AF XY:
AC XY:
10
AN XY:
135920
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000561 AC: 82AN: 1461874Hom.: 0 Cov.: 33 AF XY: 0.0000536 AC XY: 39AN XY: 727238
GnomAD4 exome
AF:
AC:
82
AN:
1461874
Hom.:
Cov.:
33
AF XY:
AC XY:
39
AN XY:
727238
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.000237 AC: 36AN: 152118Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16AN XY: 74304
GnomAD4 genome
AF:
AC:
36
AN:
152118
Hom.:
Cov.:
32
AF XY:
AC XY:
16
AN XY:
74304
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
0
ESP6500EA
AF:
AC:
1
ExAC
AF:
AC:
5
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 24, 2021 | The c.1810G>A (p.D604N) alteration is located in exon 16 (coding exon 15) of the STAT6 gene. This alteration results from a G to A substitution at nucleotide position 1810, causing the aspartic acid (D) at amino acid position 604 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Pathogenic
D;.;D;D;.;D;T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
.;.;.;.;T;T;T;.
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T;T;T;T
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;.;M;M;.;M;.;.
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D;D;D;D;D;.
REVEL
Pathogenic
Sift
Uncertain
D;T;D;D;T;D;D;.
Sift4G
Pathogenic
D;D;D;D;D;D;D;.
Polyphen
D;.;D;D;.;D;.;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at