12-57096593-TAG-CAA

Variant names:

• chr12-57096593-TAG-CAA
• NM_003153.5:c.2521_2523delCTAinsTTG
• STAT6 p.842

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_003153.5(STAT6):​c.2521_2523delCTAinsTTG​(p.842) variant causes a synonymous change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: STAT6 NM_003153.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.26
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• hyper-IgE syndrome 6, autosomal dominant, with recurrent infections

  Inheritance: AD Classification: STRONG Submitted by: ClinGen, PanelApp Australia

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003153.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAT6	NM_003153.5	MANE Select	c.2521_2523delCTAinsTTG	p.842	synonymous	N/A	NP_003144.3
	STAT6	NM_001178078.2		c.2521_2523delCTAinsTTG	p.842	synonymous	N/A	NP_001171549.1	P42226-1
	STAT6	NM_001178079.2		c.2521_2523delCTAinsTTG	p.842	synonymous	N/A	NP_001171550.1	P42226-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAT6	ENST00000300134.8	TSL:1 MANE Select	c.2521_2523delCTAinsTTG	p.842	synonymous	N/A	ENSP00000300134.3	P42226-1
	STAT6	ENST00000556155.5	TSL:1	c.2521_2523delCTAinsTTG	p.842	synonymous	N/A	ENSP00000451742.1	P42226-1
	STAT6	ENST00000553533.2	TSL:3	c.2575_2577delCTAinsTTG	p.860	synonymous	N/A	ENSP00000451546.2	H0YJH6

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-57490376;