Variant 16-11254919-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate

The NM_003745.2(SOCS1):c.560G>A(p.Gly187Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000225 in 1,334,368 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

SOCS1
NM_003745.2 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 7.36

Variant links:

Genes affected

SOCS1 (HGNC:19383): (suppressor of cytokine signaling 1) 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 can be induced by a subset of cytokines, including IL2, IL3 erythropoietin (EPO), CSF2/GM-CSF, and interferon (IFN)-gamma. The protein encoded by this gene functions downstream of cytokine receptors, and takes part in a negative feedback loop to attenuate cytokine signaling. Knockout studies in mice suggested the role of this gene as a modulator of IFN-gamma action, which is required for normal postnatal growth and survival. [provided by RefSeq, Jul 2008]

SOCS1 links:

RMI2 (HGNC:28349): (RecQ mediated genome instability 2) RMI2 is a component of the BLM (RECQL3; MIM 604610) complex, which plays a role in homologous recombination-dependent DNA repair and is essential for genome stability (Xu et al., 2008 [PubMed 18923082]).[supplied by OMIM, Nov 2008]

RMI2 links:

RMI2 (HGNC:):

RMI2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 16-11254919-C-T is Pathogenic according to our data. Variant chr16-11254919-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2627601.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOCS1	NM_003745.2 linkuse as main transcript	c.560G>A	p.Gly187Asp	missense_variant	2/2	ENST00000332029.4	NP_003736.1	O15524Q4JHT5
LOC105371082	XR_933070.4 linkuse as main transcript	n.178+5141C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOCS1	ENST00000332029.4 linkuse as main transcript	c.560G>A	p.Gly187Asp	missense_variant	2/2	1	NM_003745.2	ENSP00000329418.2		O15524

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000225

AC:

AN:

1334368

Hom.:

Cov.:

AF XY:

0.00000303

AC XY:

AN XY:

659228

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000189

Gnomad4 OTH exome

AF:

0.0000183

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Autoinflammatory syndrome with immunodeficiency

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Institute of Human Genetics, University of Leipzig Medical Center

Oct 04, 2023

Criteria applied: PM2_SUP,PP3, PS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.89

BayesDel_addAF

Benign

0.0015

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.54

D;D

Eigen

Benign

0.079

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.83

.;T

M_CAP

Benign

0.042

MetaRNN

Uncertain

0.53

D;D

MetaSVM

Benign

-0.82

MutationAssessor

Benign

1.8

L;L

PrimateAI

Pathogenic

0.91

PROVEAN

Uncertain

-3.9

D;.

REVEL

Benign

0.21

Sift

Benign

0.12

T;.

Sift4G

Benign

0.12

T;.

Polyphen

0.084

B;B

Vest4

0.88

MutPred

0.53

Loss of MoRF binding (P = 0.0269);Loss of MoRF binding (P = 0.0269);

MVP

0.62

MPC

2.1

ClinPred

0.99

GERP RS

4.3

Varity_R

0.63

gMVP

0.73

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over