Variant 17-38352304-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014598.4(SOCS7):c.252G>T(p.Glu84Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000748 in 1,336,424 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: not found (cov: 33)

Exomes 𝑓: 7.5e-7 ( 0 hom. )

Consequence

SOCS7
NM_014598.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0690

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 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=0.09838134).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOCS7	NM_014598.4 linkuse as main transcript	c.252G>T	p.Glu84Asp	missense_variant	1/10	ENST00000612932.6	NP_055413.2	O14512
SOCS7	XM_017024551.2 linkuse as main transcript	c.252G>T	p.Glu84Asp	missense_variant	1/9		XP_016880040.1
SOCS7	XM_017024552.2 linkuse as main transcript	c.252G>T	p.Glu84Asp	missense_variant	1/8		XP_016880041.1
SOCS7	XR_007065295.1 linkuse as main transcript	n.461G>T		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.252G>T	p.Glu84Asp	missense_variant	1/10	1	NM_014598.4	ENSP00000482229.2	A0A5F9YLF9
SOCS7	ENST00000665913.1 linkuse as main transcript	c.60G>T	p.Glu20Asp	missense_variant	1/10			ENSP00000499750.1	O14512-1
SOCS7	ENST00000613678.5 linkuse as main transcript	c.75G>T	p.Glu25Asp	missense_variant	1/9	5		ENSP00000484381.2	A0A087X1Q5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.48e-7

AC:

AN:

1336424

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

660652

show subpopulations

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:

9.42e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Apr 07, 2023

The c.60G>T (p.E20D) alteration is located in exon 1 (coding exon 1) of the SOCS7 gene. This alteration results from a G to T substitution at nucleotide position 60, causing the glutamic acid (E) at amino acid position 20 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

Benign

0.084

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.19

.;T

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.17

M_CAP

Pathogenic

0.52

MetaRNN

Benign

0.098

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

.;N

PrimateAI

Pathogenic

0.94

Sift4G

Benign

0.41

T;T

Polyphen

0.013

.;B

Vest4

0.080

MutPred

0.11

Loss of glycosylation at P23 (P = 0.1134);Loss of glycosylation at P23 (P = 0.1134);

MVP

0.39

ClinPred

0.15

GERP RS

1.2

Varity_R

0.11

gMVP

0.10

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over