17-38352881-C-A

Variant names:

• chr17-38352881-C-A
• rs1328005893
• NM_014598.4:c.829C>A

Variant summary

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

The NM_014598.4(SOCS7):​c.829C>A​(p.Arg277Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R277C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SOCS7 NM_014598.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.78
• Publications: 0 publications found

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]

ACMG classification

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>A	p.Arg277Ser	missense	Exon 1 of 10	NP_055413.2	A0A5F9YLF9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOCS7	ENST00000612932.6	TSL:1 MANE Select	c.829C>A	p.Arg277Ser	missense	Exon 1 of 10	ENSP00000482229.2	A0A5F9YLF9
	SOCS7	ENST00000665913.1		c.637C>A	p.Arg213Ser	missense	Exon 1 of 10	ENSP00000499750.1	O14512-1
	SOCS7	ENST00000613678.5	TSL:5	c.652C>A	p.Arg218Ser	missense	Exon 1 of 9	ENSP00000484381.2	A0A087X1Q5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1444456 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 716728

African (AFR) AF: 0.00 AC: 0 AN: 33252

American (AMR) AF: 0.00 AC: 0 AN: 42470

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25654

East Asian (EAS) AF: 0.00 AC: 0 AN: 39052

South Asian (SAS) AF: 0.00 AC: 0 AN: 83078

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51016

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1104536

Other (OTH) AF: 0.00 AC: 0 AN: 59680

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	29
DANN	Benign	0.94
DEOGEN2	Uncertain	0.45	T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Benign	0.60	D
M_CAP	Pathogenic	0.57	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.52	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		1.8
PrimateAI	Pathogenic	0.86	D
Sift4G	Benign	0.26	T
Polyphen		0.88	P
Vest4		0.70
MutPred		0.39		Gain of phosphorylation at R213 (P = 0.0219)
MVP		0.90
ClinPred		0.77	D
GERP RS		3.5
PromoterAI		-0.024	Neutral
Varity_R		0.27
gMVP		0.65

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

Other links and lift over

dbSNP: rs1328005893; hg19: chr17-36508764;