2-46758586-T-A

Position:

• chr2-46758586-T-A

Variant summary

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

The NM_144949.3(SOCS5):​c.56T>A​(p.Phe19Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SOCS5 NM_144949.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.53

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:):

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/exons	MANE	Protein	UniProt
SOCS5	NM_144949.3	c.56T>A	p.Phe19Tyr	missense_variant	2/2	ENST00000394861.3	NP_659198.1
SOCS5	NM_014011.5	c.56T>A	p.Phe19Tyr	missense_variant	2/2		NP_054730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOCS5	ENST00000394861.3	c.56T>A	p.Phe19Tyr	missense_variant	2/2	1	NM_144949.3	ENSP00000378330.2
SOCS5	ENST00000306503.5	c.56T>A	p.Phe19Tyr	missense_variant	2/2	1		ENSP00000305133.5
LINC01118	ENST00000650611.1	n.173-38733T>A		intron_variant

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 26, 2023

The c.56T>A (p.F19Y) alteration is located in exon 2 (coding exon 1) of the SOCS5 gene. This alteration results from a T to A substitution at nucleotide position 56, causing the phenylalanine (F) at amino acid position 19 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Uncertain	0.045	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T;T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.72	.;T
M_CAP	Benign	0.0096	T
MetaRNN	Uncertain	0.71	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;L
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	0.070	N;N
REVEL	Benign	0.21
Sift	Uncertain	0.0070	D;D
Sift4G	Uncertain	0.046	D;D
Polyphen		0.96	D;D
Vest4		0.68
MutPred		0.51		Gain of MoRF binding (P = 0.1095);Gain of MoRF binding (P = 0.1095);
MVP		0.39
MPC		0.60
ClinPred		0.76	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.30
gMVP		0.35

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: chr2-46985725;