rs368272800

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr2-46758624-A-C
• chr2-46758624-A-G
• chr2-46758624-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_144949.3(SOCS5):​c.94A>C​(p.Met32Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SOCS5 NM_144949.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059533566).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOCS5	NM_144949.3	c.94A>C	p.Met32Leu	missense_variant	Exon 2 of 2	ENST00000394861.3	NP_659198.1
SOCS5	NM_014011.5	c.94A>C	p.Met32Leu	missense_variant	Exon 2 of 2		NP_054730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOCS5	ENST00000394861.3	c.94A>C	p.Met32Leu	missense_variant	Exon 2 of 2	1	NM_144949.3	ENSP00000378330.2
SOCS5	ENST00000306503.5	c.94A>C	p.Met32Leu	missense_variant	Exon 2 of 2	1		ENSP00000305133.5
LINC01118	ENST00000650611.1	n.173-38695A>C		intron_variant	Intron 1 of 7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461686 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727164

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000180

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	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;T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.75
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.63	.;T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.060	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.29	N;N
REVEL	Benign	0.040
Sift	Benign	0.44	T;T
Sift4G	Benign	0.59	T;T
Polyphen		0.0	B;B
Vest4		0.12
MutPred		0.16		Loss of disorder (P = 0.1697);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

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: chr2-46985763;