17-78358808-C-T

Variant names:

• chr17-78358808-C-T
• rs12059
• NM_003955.5:c.288G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_003955.5(SOCS3):​c.288G>A​(p.Gln96Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SOCS3 NM_003955.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.19
• Publications: 3 publications found

Genes affected

SOCS3 (HGNC:19391): (suppressor of cytokine signaling 3) This gene encodes a member of the STAT-induced STAT inhibitor (SSI), also known as suppressor of cytokine signaling (SOCS), family. SSI family members are cytokine-inducible negative regulators of cytokine signaling. The expression of this gene is induced by various cytokines, including IL6, IL10, and interferon (IFN)-gamma. The protein encoded by this gene can bind to JAK2 kinase, and inhibit the activity of JAK2 kinase. Studies of the mouse counterpart of this gene suggested the roles of this gene in the negative regulation of fetal liver hematopoiesis, and placental development. [provided by RefSeq, Jul 2008]

SOCS3-DT (HGNC:52799): (SOCS3 divergent transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP7: Synonymous conserved (PhyloP=3.19 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003955.5. 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
	SOCS3	NM_003955.5	MANE Select	c.288G>A	p.Gln96Gln	synonymous	Exon 2 of 2	NP_003946.3
	SOCS3	NM_001378932.1		c.288G>A	p.Gln96Gln	synonymous	Exon 2 of 2	NP_001365861.1	O14543
	SOCS3	NM_001378933.1		c.288G>A	p.Gln96Gln	synonymous	Exon 2 of 2	NP_001365862.1	O14543

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOCS3	ENST00000330871.3	TSL:1 MANE Select	c.288G>A	p.Gln96Gln	synonymous	Exon 2 of 2	ENSP00000330341.2	O14543
	SOCS3	ENST00000907726.1		c.288G>A	p.Gln96Gln	synonymous	Exon 2 of 2	ENSP00000577785.1
	SOCS3	ENST00000912407.1		c.288G>A	p.Gln96Gln	synonymous	Exon 3 of 3	ENSP00000582466.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	14
DANN	Benign	0.97
PhyloP100		3.2

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

Other links and lift over

dbSNP: rs12059; hg19: chr17-76354889;