Genetic Variant NM_014598.4:c.829C>T (chr17-38352881-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014598.4(SOCS7):c.829C>T(p.Arg277Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000188 in 1,596,674 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SOCS7
NM_014598.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.78

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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.829C>T	p.Arg277Cys	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.829C>T	p.Arg277Cys	missense	Exon 1 of 10	ENSP00000482229.2	A0A5F9YLF9
SOCS7	ENST00000665913.1		c.637C>T	p.Arg213Cys	missense	Exon 1 of 10	ENSP00000499750.1	O14512-1
SOCS7	ENST00000613678.5	TSL:5	c.652C>T	p.Arg218Cys	missense	Exon 1 of 9	ENSP00000484381.2	A0A087X1Q5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1444458

Hom.:

Cov.:

AF XY:

0.00000279

AC XY:

AN XY:

716728

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33252

American (AMR)

AF:

0.00

AC:

AN:

42470

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25654

East Asian (EAS)

AF:

0.0000256

AC:

AN:

39054

South Asian (SAS)

AF:

0.00

AC:

AN:

83078

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51016

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5718

European-Non Finnish (NFE)

AF:

9.05e-7

AC:

AN:

1104536

Other (OTH)

AF:

0.00

AC:

AN:

59680

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

AF:

0.00000657

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41464

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000113

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

Pathogenic

0.65

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.010

CADD

Pathogenic

(source)

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.62

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.0023

FATHMM_MKL

Benign

0.53

M_CAP

Pathogenic

0.53

MetaRNN

Uncertain

0.65

MetaSVM

Benign

-0.66

MutationAssessor

Uncertain

2.0

PhyloP100

1.8

PrimateAI

Pathogenic

0.89

Sift4G

Uncertain

0.043

Polyphen

0.10

Vest4

0.69

MutPred

0.46

Loss of sheet (P = 0.0181)

MVP

0.90

ClinPred

0.69

GERP RS

3.5

PromoterAI

-0.065

Neutral

(source)

Varity_R

0.18

gMVP

0.59

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over