chr17-78360015-T-G

Variant names:

• chr17-78360015-T-G
• rs12953258
• NM_003955.5:c.-354A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003955.5(SOCS3):​c.-354A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.9 in 201,872 control chromosomes in the GnomAD database, including 82,065 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 0.91 (62760 hom., cov: 35)
  • Exomes 𝑓: 0.87 (19305 hom.)
• Consequence: SOCS3 NM_003955.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75
• Publications: 25 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

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.-354A>C		5_prime_UTR	Exon 1 of 2	NP_003946.3
	SOCS3	NM_001378933.1		c.-88-832A>C		intron	N/A	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.-354A>C		5_prime_UTR	Exon 1 of 2	ENSP00000330341.2	O14543
	SOCS3	ENST00000587578.1	TSL:4	c.-255A>C		5_prime_UTR	Exon 1 of 2	ENSP00000464727.1	K7EIF6
	SOCS3	ENST00000912407.1		c.-179-175A>C		intron	N/A	ENSP00000582466.1

Frequencies

GnomAD3 genomes AF: 0.908 AC: 137693 AN: 151622 Hom.: 62707 Cov.: 35

Gnomad AFR AF: 0.936

Gnomad AMI AF: 0.897

Gnomad AMR AF: 0.893

Gnomad ASJ AF: 0.893

Gnomad EAS AF: 0.683

Gnomad SAS AF: 0.946

Gnomad FIN AF: 0.896

Gnomad MID AF: 0.939

Gnomad NFE AF: 0.912

Gnomad OTH AF: 0.894

GnomAD4 exome AF: 0.875 AC: 43851 AN: 50142 Hom.: 19305 Cov.: 0 AF XY: 0.876 AC XY: 23133 AN XY: 26410

African (AFR) AF: 0.927 AC: 871 AN: 940

American (AMR) AF: 0.847 AC: 878 AN: 1036

Ashkenazi Jewish (ASJ) AF: 0.866 AC: 1157 AN: 1336

East Asian (EAS) AF: 0.683 AC: 3785 AN: 5538

South Asian (SAS) AF: 0.956 AC: 939 AN: 982

European-Finnish (FIN) AF: 0.879 AC: 5766 AN: 6562

Middle Eastern (MID) AF: 0.931 AC: 216 AN: 232

European-Non Finnish (NFE) AF: 0.904 AC: 27987 AN: 30954

Other (OTH) AF: 0.879 AC: 2252 AN: 2562

GnomAD4 genome AF: 0.908 AC: 137801 AN: 151730 Hom.: 62760 Cov.: 35 AF XY: 0.907 AC XY: 67263 AN XY: 74156

African (AFR) AF: 0.936 AC: 38807 AN: 41476

American (AMR) AF: 0.893 AC: 13615 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.893 AC: 3098 AN: 3470

East Asian (EAS) AF: 0.683 AC: 3500 AN: 5122

South Asian (SAS) AF: 0.946 AC: 4569 AN: 4832

European-Finnish (FIN) AF: 0.896 AC: 9331 AN: 10412

Middle Eastern (MID) AF: 0.938 AC: 272 AN: 290

European-Non Finnish (NFE) AF: 0.912 AC: 61908 AN: 67868

Other (OTH) AF: 0.895 AC: 1885 AN: 2106

Alfa AF: 0.887 Hom.: 2841

Bravo AF: 0.903

Asia WGS AF: 0.842 AC: 2834 AN: 3364

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	10
DANN	Benign	0.42
PhyloP100		-1.8
PromoterAI		-0.015	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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: rs12953258; hg19: chr17-76356096;