Genetic Variant NM_003955.5:c.*589A>G (chr17-78357829-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003955.5(SOCS3):c.*589A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.916 in 152,564 control chromosomes in the GnomAD database, including 64,266 homozygotes. 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: 𝑓 0.92 ( 64110 hom., cov: 31)

Exomes 𝑓: 0.92 ( 156 hom. )

Consequence

SOCS3
NM_003955.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.69

Publications

19 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SOCS3	NM_003955.5 link	c.*589A>G	3_prime_UTR_variant	Exon 2 of 2	ENST00000330871.3	NP_003946.3	O14543Q6FI39
SOCS3	NM_001378932.1 link	c.*589A>G	3_prime_UTR_variant	Exon 2 of 2		NP_001365861.1
SOCS3	NM_001378933.1 link	c.*589A>G	3_prime_UTR_variant	Exon 2 of 2		NP_001365862.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOCS3	ENST00000330871.3 link	c.*589A>G		3_prime_UTR_variant	Exon 2 of 2	1	NM_003955.5	ENSP00000330341.2		O14543
SOCS3-DT	ENST00000794159.1 link	n.208-167T>C		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.916

AC:

139354

AN:

152078

Hom.:

64053

Cov.:

show subpopulations

Gnomad AFR

AF:

0.942

Gnomad AMI

AF:

0.929

Gnomad AMR

AF:

0.904

Gnomad ASJ

AF:

0.904

Gnomad EAS

AF:

0.684

Gnomad SAS

AF:

0.945

Gnomad FIN

AF:

0.898

Gnomad MID

AF:

0.946

Gnomad NFE

AF:

0.923

Gnomad OTH

AF:

0.902

GnomAD4 exome

AF:

0.921

AC:

337

AN:

366

Hom.:

156

Cov.:

AF XY:

0.944

AC XY:

234

AN XY:

248

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AF:

0.917

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.333

AC:

AN:

South Asian (SAS)

AF:

0.967

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.925

AC:

209

AN:

226

Other (OTH)

AF:

0.778

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.916

AC:

139471

AN:

152198

Hom.:

64110

Cov.:

AF XY:

0.915

AC XY:

68048

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.942

AC:

39124

AN:

41534

American (AMR)

AF:

0.904

AC:

13819

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.904

AC:

3140

AN:

3472

East Asian (EAS)

AF:

0.684

AC:

3511

AN:

5136

South Asian (SAS)

AF:

0.944

AC:

4548

AN:

4816

European-Finnish (FIN)

AF:

0.898

AC:

9520

AN:

10600

Middle Eastern (MID)

AF:

0.946

AC:

278

AN:

294

European-Non Finnish (NFE)

AF:

0.923

AC:

62777

AN:

68028

Other (OTH)

AF:

0.903

AC:

1907

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

582

1163

1745

2326

2908

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

904

1808

2712

3616

4520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.912

Hom.:

58728

Bravo

AF:

0.913

Asia WGS

AF:

0.856

AC:

2978

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.5

(source)

DANN

Benign

0.49

PhyloP100

-1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over