Variant 17-38352554-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_014598.4(SOCS7):c.502G>C(p.Gly168Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000503 in 1,549,508 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00037 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00052 ( 1 hom. )

Consequence

SOCS7
NM_014598.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.575

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11039576).

BS2

High AC in GnomAd4 at 57 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOCS7	NM_014598.4 linkuse as main transcript	c.502G>C	p.Gly168Arg	missense_variant	1/10	ENST00000612932.6	NP_055413.2	O14512
SOCS7	XM_017024551.2 linkuse as main transcript	c.502G>C	p.Gly168Arg	missense_variant	1/9		XP_016880040.1
SOCS7	XM_017024552.2 linkuse as main transcript	c.502G>C	p.Gly168Arg	missense_variant	1/8		XP_016880041.1
SOCS7	XR_007065295.1 linkuse as main transcript	n.711G>C		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.502G>C	p.Gly168Arg	missense_variant	1/10	1	NM_014598.4	ENSP00000482229.2	A0A5F9YLF9
SOCS7	ENST00000665913.1 linkuse as main transcript	c.310G>C	p.Gly104Arg	missense_variant	1/10			ENSP00000499750.1	O14512-1
SOCS7	ENST00000613678.5 linkuse as main transcript	c.325G>C	p.Gly109Arg	missense_variant	1/9	5		ENSP00000484381.2	A0A087X1Q5
SOCS7	ENST00000617360.1 linkuse as main transcript	n.4G>C		non_coding_transcript_exon_variant	1/9	5

Frequencies

GnomAD3 genomes

AF:

0.000375

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000343

AC:

AN:

142962

Hom.:

AF XY:

0.000298

AC XY:

AN XY:

77192

show subpopulations

Gnomad AFR exome

AF:

0.000145

Gnomad AMR exome

AF:

0.0000408

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000461

Gnomad NFE exome

AF:

0.000790

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000517

AC:

722

AN:

1397198

Hom.:

Cov.:

AF XY:

0.000515

AC XY:

355

AN XY:

689026

show subpopulations

Gnomad4 AFR exome

AF:

0.0000633

Gnomad4 AMR exome

AF:

0.0000841

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000776

Gnomad4 NFE exome

AF:

0.000607

Gnomad4 OTH exome

AF:

0.000431

GnomAD4 genome

AF:

0.000374

AC:

AN:

152310

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0000721

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000609

Hom.:

Bravo

AF:

0.000325

ExAC

AF:

0.0000663

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

May 30, 2024

The c.310G>C (p.G104R) alteration is located in exon 1 (coding exon 1) of the SOCS7 gene. This alteration results from a G to C substitution at nucleotide position 310, causing the glycine (G) at amino acid position 104 to be replaced by an arginine (R). 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

0.24

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.40

CADD

Pathogenic

DANN

Benign

0.96

DEOGEN2

Benign

0.36

.;T

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.21

FATHMM_MKL

Uncertain

0.76

M_CAP

Pathogenic

0.86

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

.;L

PrimateAI

Pathogenic

0.90

Sift4G

Uncertain

0.016

D;D

Polyphen

0.33

.;B

Vest4

0.18

MutPred

0.12

Gain of helix (P = 0.0496);Gain of helix (P = 0.0496);

MVP

0.38

ClinPred

0.16

GERP RS

1.6

Varity_R

0.13

gMVP

0.45

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

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