2-46758931-G-C

Variant names:

• chr2-46758931-G-C
• rs758655262
• NM_144949.3:c.401G>C

Variant summary

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

The NM_144949.3(SOCS5):​c.401G>C​(p.Ser134Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. S134N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SOCS5 NM_144949.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.29
• Publications: 0 publications found

Genes affected

SOCS5 (HGNC:16852): (suppressor of cytokine signaling 5) The protein encoded by this gene contains a SH2 domain and a SOCS BOX domain. The protein thus belongs to the suppressor of cytokine signaling (SOCS) family, also known as STAT-induced STAT inhibitor (SSI) protein family. SOCS family members are known to be cytokine-inducible negative regulators of cytokine signaling. The specific function of this protein has not yet been determined. Two alternatively spliced transcript variants encoding an identical protein have been reported. [provided by RefSeq, Jul 2008]

LINC01118 (HGNC:49261): (long intergenic non-protein coding RNA 1118)

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=0.19956908).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144949.3. 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
	SOCS5	NM_144949.3	MANE Select	c.401G>C	p.Ser134Thr	missense	Exon 2 of 2	NP_659198.1	O75159
	SOCS5	NM_014011.5		c.401G>C	p.Ser134Thr	missense	Exon 2 of 2	NP_054730.1	O75159

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOCS5	ENST00000394861.3	TSL:1 MANE Select	c.401G>C	p.Ser134Thr	missense	Exon 2 of 2	ENSP00000378330.2	O75159
	SOCS5	ENST00000306503.5	TSL:1	c.401G>C	p.Ser134Thr	missense	Exon 2 of 2	ENSP00000305133.5	O75159
	SOCS5	ENST00000861862.1		c.401G>C	p.Ser134Thr	missense	Exon 2 of 2	ENSP00000531921.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.41	T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		6.3
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.089
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.091	T
Polyphen		0.46	P
Vest4		0.35
MutPred		0.15		Gain of relative solvent accessibility (P = 0.0215)
MVP		0.43
MPC		0.13
ClinPred		0.82	D
GERP RS		5.4
Varity_R		0.45
gMVP		0.27
Mutation Taster		=78/22	polymorphism

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: rs758655262; hg19: chr2-46986070;