17-38352443-C-A

Position:

• chr17-38352443-C-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.391C>A​(p.Gln131Lys) 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. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SOCS7 NM_014598.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.515

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]

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=0.15017784).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOCS7	NM_014598.4	c.391C>A	p.Gln131Lys	missense_variant	1/10	ENST00000612932.6	NP_055413.2
SOCS7	XM_017024551.2	c.391C>A	p.Gln131Lys	missense_variant	1/9		XP_016880040.1
SOCS7	XM_017024552.2	c.391C>A	p.Gln131Lys	missense_variant	1/8		XP_016880041.1
SOCS7	XR_007065295.1	n.600C>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.391C>A	p.Gln131Lys	missense_variant	1/10	1	NM_014598.4	ENSP00000482229.2
SOCS7	ENST00000665913.1	c.199C>A	p.Gln67Lys	missense_variant	1/10			ENSP00000499750.1
SOCS7	ENST00000613678.5	c.214C>A	p.Gln72Lys	missense_variant	1/9	5		ENSP00000484381.2

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

Aug 01, 2023

The c.199C>A (p.Q67K) alteration is located in exon 1 (coding exon 1) of the SOCS7 gene. This alteration results from a C to A substitution at nucleotide position 199, causing the glutamine (Q) at amino acid position 67 to be replaced by a lysine (K). 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	Benign	0.15
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	20
DANN	Benign	0.94
DEOGEN2	Benign	0.19	.;T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.53	D
M_CAP	Pathogenic	0.65	D
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	.;N
PrimateAI	Pathogenic	0.89	D
Sift4G	Benign	0.94	T;T
Polyphen		0.020	.;B
Vest4		0.23
MutPred		0.20		Gain of ubiquitination at Q67 (P = 0.0051);Gain of ubiquitination at Q67 (P = 0.0051);
MVP		0.26
ClinPred		0.21	T
GERP RS		3.4
Varity_R		0.13
gMVP		0.17

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: chr17-36508326;