chr17-78358808-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003955.5(SOCS3):​c.288G>C​(p.Gln96His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,460,924 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SOCS3 NM_003955.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.19

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOCS3	NM_003955.5	c.288G>C	p.Gln96His	missense_variant	Exon 2 of 2	ENST00000330871.3	NP_003946.3
SOCS3	NM_001378932.1	c.288G>C	p.Gln96His	missense_variant	Exon 2 of 2		NP_001365861.1
SOCS3	NM_001378933.1	c.288G>C	p.Gln96His	missense_variant	Exon 2 of 2		NP_001365862.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOCS3	ENST00000330871.3	c.288G>C	p.Gln96His	missense_variant	Exon 2 of 2	1	NM_003955.5	ENSP00000330341.2
SOCS3	ENST00000587578.1	c.*241G>C		downstream_gene_variant		4		ENSP00000464727.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1460924 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726784

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Uncertain	0.048	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	23
DANN	Benign	0.96
DEOGEN2	Uncertain	0.67	D
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.049
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.82	T
M_CAP	Pathogenic	0.50	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Benign	0.82	L
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.88	N
REVEL	Uncertain	0.30
Sift	Benign	0.26	T
Sift4G	Benign	0.34	T
Polyphen		0.15	B
Vest4		0.18
MutPred		0.54		Loss of ubiquitination at K91 (P = 0.0672);
MVP		0.71
MPC		1.1
ClinPred		0.56	D
GERP RS		4.1
Varity_R		0.25
gMVP		0.67

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.

Other links and lift over

hg19: chr17-76354889;