Variant chr12-57100014-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_003153.5(STAT6):c.1589G>A(p.Arg530Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000178 in 1,461,082 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: not found (cov: 31)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

STAT6
NM_003153.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.18

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]

STAT6 links:

STAT6 (HGNC:):

STAT6 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.34127915).

BS2

High AC in GnomAdExome4 at 26 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAT6	NM_003153.5 linkuse as main transcript	c.1589G>A	p.Arg530Gln	missense_variant	14/22	ENST00000300134.8	NP_003144.3	P42226-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAT6	ENST00000300134.8 linkuse as main transcript	c.1589G>A	p.Arg530Gln	missense_variant	14/22	1	NM_003153.5	ENSP00000300134.3		P42226-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000803

AC:

AN:

249044

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

134636

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000547

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000889

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000178

AC:

AN:

1461082

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

726768

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000198

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Apr 25, 2023

The c.1589G>A (p.R530Q) alteration is located in exon 14 (coding exon 13) of the STAT6 gene. This alteration results from a G to A substitution at nucleotide position 1589, causing the arginine (R) at amino acid position 530 to be replaced by a glutamine (Q). 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

0.18

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.50

D;.;D;D;.;D;.;T

Eigen

Benign

0.057

Eigen_PC

Benign

0.12

FATHMM_MKL

Benign

0.58

LIST_S2

Uncertain

0.90

.;.;.;.;D;D;.;.

M_CAP

Benign

0.080

MetaRNN

Benign

0.34

T;T;T;T;T;T;T;T

MetaSVM

Uncertain

0.071

MutationAssessor

Benign

0.75

N;.;N;N;.;N;.;.

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.9

N;N;N;N;N;N;.;N

REVEL

Uncertain

0.43

Sift

Benign

0.066

T;T;T;T;T;T;.;T

Sift4G

Benign

0.087

T;T;T;T;T;T;.;.

Polyphen

0.57

P;.;P;P;.;P;.;.

Vest4

0.28

MutPred

0.46

Loss of MoRF binding (P = 0.0268);.;Loss of MoRF binding (P = 0.0268);Loss of MoRF binding (P = 0.0268);.;Loss of MoRF binding (P = 0.0268);Loss of MoRF binding (P = 0.0268);.;

MVP

0.95

MPC

0.60

ClinPred

0.45

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.23

gMVP

0.60

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over