Genetic Variant NM_014598.4:c.653C>G (chr17-38352705-C-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_014598.4(SOCS7):c.653C>G(p.Pro218Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000859 in 1,397,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 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: 0.0000086 ( 0 hom. )

Consequence

SOCS7
NM_014598.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.765

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12466973).

BS2

High AC in GnomAdExome4 at 12 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014598.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOCS7	NM_014598.4	MANE Select	c.653C>G	p.Pro218Arg	missense	Exon 1 of 10	NP_055413.2	A0A5F9YLF9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SOCS7	ENST00000612932.6	TSL:1 MANE Select	c.653C>G	p.Pro218Arg	missense	Exon 1 of 10	ENSP00000482229.2	A0A5F9YLF9
SOCS7	ENST00000665913.1		c.461C>G	p.Pro154Arg	missense	Exon 1 of 10	ENSP00000499750.1	O14512-1
SOCS7	ENST00000613678.5	TSL:5	c.476C>G	p.Pro159Arg	missense	Exon 1 of 9	ENSP00000484381.2	A0A087X1Q5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000136

AC:

AN:

147554

AF XY:

0.0000252

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000471

GnomAD4 exome

AF:

0.00000859

AC:

AN:

1397644

Hom.:

Cov.:

AF XY:

0.0000116

AC XY:

AN XY:

689314

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31594

American (AMR)

AF:

0.00

AC:

AN:

35700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25166

East Asian (EAS)

AF:

0.0000280

AC:

AN:

35732

South Asian (SAS)

AF:

0.00

AC:

AN:

79216

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47804

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5602

European-Non Finnish (NFE)

AF:

0.00000185

AC:

AN:

1078872

Other (OTH)

AF:

0.000155

AC:

AN:

57958

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.090

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.23

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.61

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

PhyloP100

0.77

PrimateAI

Pathogenic

0.82

Sift4G

Uncertain

0.036

Polyphen

0.72

Vest4

0.29

MutPred

0.22

Loss of catalytic residue at P154 (P = 0.004)

MVP

0.39

ClinPred

0.11

GERP RS

3.2

PromoterAI

0.060

Neutral

(source)

Varity_R

0.059

gMVP

0.35

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over