17-78358987-C-A

Variant names:

• chr17-78358987-C-A
• rs942037936
• NM_003955.5:c.109G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003955.5(SOCS3):​c.109G>T​(p.Ala37Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000019 in 1,576,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A37T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SOCS3 NM_003955.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.64
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26174003).

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.109G>T	p.Ala37Ser	missense	Exon 2 of 2	NP_003946.3
	SOCS3	NM_001378932.1		c.109G>T	p.Ala37Ser	missense	Exon 2 of 2	NP_001365861.1	O14543
	SOCS3	NM_001378933.1		c.109G>T	p.Ala37Ser	missense	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.109G>T	p.Ala37Ser	missense	Exon 2 of 2	ENSP00000330341.2	O14543
	SOCS3	ENST00000907726.1		c.109G>T	p.Ala37Ser	missense	Exon 2 of 2	ENSP00000577785.1
	SOCS3	ENST00000912407.1		c.109G>T	p.Ala37Ser	missense	Exon 3 of 3	ENSP00000582466.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152092 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000527 AC: 1 AN: 189848 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000357

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1424790 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 705080

African (AFR) AF: 0.00 AC: 0 AN: 32768

American (AMR) AF: 0.0000254 AC: 1 AN: 39296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25378

East Asian (EAS) AF: 0.00 AC: 0 AN: 37996

South Asian (SAS) AF: 0.00 AC: 0 AN: 81884

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49916

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5706

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1092900

Other (OTH) AF: 0.0000170 AC: 1 AN: 58946

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152092 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74286

African (AFR) AF: 0.0000241 AC: 1 AN: 41410

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.53	D
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.29
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.83	T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.6
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.13
Sift	Uncertain	0.022	D
Sift4G	Benign	0.088	T
Polyphen		0.45	B
Vest4		0.20
MutPred		0.31		Gain of disorder (P = 0.0475)
MVP		0.48
MPC		1.9
ClinPred		0.38	T
GERP RS		2.0
Varity_R		0.15
gMVP		0.34

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: rs942037936; hg19: chr17-76355068;