Variant 17-38352461-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_014598.4(SOCS7):c.409G>A(p.Val137Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000152 in 1,503,012 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.00082 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000076 ( 0 hom. )

Consequence

SOCS7
NM_014598.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.272

Variant links:

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 links:

SOCS7 (HGNC:):

SOCS7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0066717863).

BS2

High AC in GnomAd4 at 125 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOCS7	NM_014598.4 linkuse as main transcript	c.409G>A	p.Val137Ile	missense_variant	1/10	ENST00000612932.6	NP_055413.2	O14512
SOCS7	XM_017024551.2 linkuse as main transcript	c.409G>A	p.Val137Ile	missense_variant	1/9		XP_016880040.1
SOCS7	XM_017024552.2 linkuse as main transcript	c.409G>A	p.Val137Ile	missense_variant	1/8		XP_016880041.1
SOCS7	XR_007065295.1 linkuse as main transcript	n.618G>A		non_coding_transcript_exon_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SOCS7	ENST00000612932.6 linkuse as main transcript	c.409G>A	p.Val137Ile	missense_variant	1/10	1	NM_014598.4	ENSP00000482229.2	A0A5F9YLF9
SOCS7	ENST00000665913.1 linkuse as main transcript	c.217G>A	p.Val73Ile	missense_variant	1/10			ENSP00000499750.1	O14512-1
SOCS7	ENST00000613678.5 linkuse as main transcript	c.232G>A	p.Val78Ile	missense_variant	1/9	5		ENSP00000484381.2	A0A087X1Q5

Frequencies

GnomAD3 genomes

AF:

0.000821

AC:

125

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00249

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000252

AC:

AN:

99350

Hom.:

AF XY:

0.000170

AC XY:

AN XY:

53020

show subpopulations

Gnomad AFR exome

AF:

0.00295

Gnomad AMR exome

AF:

0.000331

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000691

GnomAD4 exome

AF:

0.0000763

AC:

103

AN:

1350718

Hom.:

Cov.:

AF XY:

0.0000589

AC XY:

AN XY:

662234

show subpopulations

Gnomad4 AFR exome

AF:

0.00250

Gnomad4 AMR exome

AF:

0.000312

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:

0.00000851

Gnomad4 OTH exome

AF:

0.000179

GnomAD4 genome

AF:

0.000821

AC:

125

AN:

152294

Hom.:

Cov.:

AF XY:

0.000765

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00248

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000435

Hom.:

Bravo

AF:

0.00116

ExAC

AF:

0.000114

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 10, 2022

The c.217G>A (p.V73I) 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 217, causing the valine (V) at amino acid position 73 to be replaced by an isoleucine (I). 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

0.087

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.67

CADD

Benign

8.9

DANN

Benign

0.96

DEOGEN2

Benign

0.20

.;T

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.022

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.0067

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;N

PrimateAI

Pathogenic

0.86

Sift4G

Benign

0.35

T;T

Polyphen

0.0070

.;B

Vest4

0.080

MutPred

0.11

Loss of catalytic residue at V73 (P = 0.1783);Loss of catalytic residue at V73 (P = 0.1783);

MVP

0.082

ClinPred

0.0023

GERP RS

1.3

Varity_R

0.021

gMVP

0.070

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over