Genetic Variant SOCS3:p.Pro148Ser (chr17-78358654-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003955.5(SOCS3):c.442C>T(p.Pro148Ser) variant causes a missense 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SOCS3
NM_003955.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.173

Publications

0 publications found

Variant links:

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 links:

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

SOCS3-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.063628405).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SOCS3	NM_003955.5	MANE Select	c.442C>T	p.Pro148Ser	missense	Exon 2 of 2	NP_003946.3
SOCS3	NM_001378932.1		c.442C>T	p.Pro148Ser	missense	Exon 2 of 2	NP_001365861.1	O14543
SOCS3	NM_001378933.1		c.442C>T	p.Pro148Ser	missense	Exon 2 of 2	NP_001365862.1	O14543

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SOCS3	ENST00000330871.3	TSL:1 MANE Select	c.442C>T	p.Pro148Ser	missense	Exon 2 of 2	ENSP00000330341.2	O14543
SOCS3	ENST00000907726.1		c.442C>T	p.Pro148Ser	missense	Exon 2 of 2	ENSP00000577785.1
SOCS3	ENST00000912407.1		c.442C>T	p.Pro148Ser	missense	Exon 3 of 3	ENSP00000582466.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1453212

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721470

African (AFR)

AF:

0.00

AC:

AN:

33342

American (AMR)

AF:

0.00

AC:

AN:

44528

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25824

East Asian (EAS)

AF:

0.00

AC:

AN:

39534

South Asian (SAS)

AF:

0.00

AC:

AN:

85856

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51910

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1106492

Other (OTH)

AF:

0.00

AC:

AN:

59984

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.38

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.62

M_CAP

Benign

0.013

MetaRNN

Benign

0.064

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.69

PhyloP100

0.17

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.31

REVEL

Benign

0.013

Sift

Benign

0.32

Sift4G

Benign

0.094

Polyphen

0.0020

Vest4

0.025

MutPred

0.24

Gain of phosphorylation at P148 (P = 0.0066)

MVP

0.23

MPC

1.1

ClinPred

0.090

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.050

gMVP

0.23

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over