chr17-38352600-G-A

Position:

• chr17-38352600-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014598.4(SOCS7):​c.548G>A​(p.Gly183Asp) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SOCS7 NM_014598.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.05

Genes affected

SOCS7 (HGNC:29846): (suppressor of cytokine signaling 7) Predicted to enable 1-phosphatidylinositol-3-kinase regulator activity. Predicted to be involved in phosphatidylinositol phosphate biosynthetic process. Predicted to act upstream of or within several processes, including brain development; fat cell differentiation; and insulin receptor signaling pathway. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

SOCS7 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14906973).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOCS7	NM_014598.4	c.548G>A	p.Gly183Asp	missense_variant	1/10	ENST00000612932.6	NP_055413.2
SOCS7	XM_017024551.2	c.548G>A	p.Gly183Asp	missense_variant	1/9		XP_016880040.1
SOCS7	XM_017024552.2	c.548G>A	p.Gly183Asp	missense_variant	1/8		XP_016880041.1
SOCS7	XR_007065295.1	n.757G>A		non_coding_transcript_exon_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOCS7	ENST00000612932.6	c.548G>A	p.Gly183Asp	missense_variant	1/10	1	NM_014598.4	ENSP00000482229.2
SOCS7	ENST00000665913.1	c.356G>A	p.Gly119Asp	missense_variant	1/10			ENSP00000499750.1
SOCS7	ENST00000613678.5	c.371G>A	p.Gly124Asp	missense_variant	1/9	5		ENSP00000484381.2
SOCS7	ENST00000617360.1	n.50G>A		non_coding_transcript_exon_variant	1/9	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

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

Nov 26, 2024

The c.356G>A (p.G119D) alteration is located in exon 1 (coding exon 1) of the SOCS7 gene. This alteration results from a G to A substitution at nucleotide position 356, causing the glycine (G) at amino acid position 119 to be replaced by an aspartic acid (D). 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	Pathogenic	0.81
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.40	.;T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.53	D
M_CAP	Pathogenic	0.68	D
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	.;N
PrimateAI	Pathogenic	0.95	D
Sift4G	Benign	0.096	T;T
Polyphen		0.19	.;B
Vest4		0.31
MutPred		0.16		Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);
MVP		0.26
ClinPred		0.30	T
GERP RS		-1.1
Varity_R		0.24
gMVP		0.58

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

LitVar

Other links and lift over

dbSNP: rs2037570486; hg19: chr17-36508483;