chr2-46758624-A-T

Variant names:

• chr2-46758624-A-T
• rs368272800
• NM_144949.3:c.94A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_144949.3(SOCS5):​c.94A>T​(p.Met32Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict 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. M32V) 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: 1.24
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05703017).

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.94A>T	p.Met32Leu	missense	Exon 2 of 2	NP_659198.1	O75159
	SOCS5	NM_014011.5		c.94A>T	p.Met32Leu	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.94A>T	p.Met32Leu	missense	Exon 2 of 2	ENSP00000378330.2	O75159
	SOCS5	ENST00000306503.5	TSL:1	c.94A>T	p.Met32Leu	missense	Exon 2 of 2	ENSP00000305133.5	O75159
	SOCS5	ENST00000861862.1		c.94A>T	p.Met32Leu	missense	Exon 2 of 2	ENSP00000531921.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	12
DANN	Benign	0.70
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.75
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	N
PhyloP100		1.2
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.040
Sift	Benign	0.44	T
Sift4G	Benign	0.59	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.16		Loss of disorder (P = 0.1697)
MVP		0.12
MPC		0.12
ClinPred		0.045	T
GERP RS		-3.0
Varity_R		0.040
gMVP		0.23
Mutation Taster		=94/6	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: rs368272800; hg19: chr2-46985763;