NM_014598.4:c.221C>T

Variant names:

• chr17-38352273-C-T
• rs1052714133
• NM_014598.4:c.221C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014598.4(SOCS7):​c.221C>T​(p.Pro74Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SOCS7 NM_014598.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.665
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19625193).

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.221C>T	p.Pro74Leu	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.221C>T	p.Pro74Leu	missense	Exon 1 of 10	ENSP00000482229.2	A0A5F9YLF9
	SOCS7	ENST00000665913.1		c.29C>T	p.Pro10Leu	missense	Exon 1 of 10	ENSP00000499750.1	O14512-1
	SOCS7	ENST00000613678.5	TSL:5	c.44C>T	p.Pro15Leu	missense	Exon 1 of 9	ENSP00000484381.2	A0A087X1Q5

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152110 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 92596 AF XY: 0.00

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: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1328200 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 656430

African (AFR) AF: 0.00 AC: 0 AN: 27240

American (AMR) AF: 0.00 AC: 0 AN: 26452

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23244

East Asian (EAS) AF: 0.00 AC: 0 AN: 29130

South Asian (SAS) AF: 0.00 AC: 0 AN: 72390

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33130

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3890

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1057550

Other (OTH) AF: 0.00 AC: 0 AN: 55174

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152110 Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3 AN XY: 74296

African (AFR) AF: 0.0000724 AC: 3 AN: 41442

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67978

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000288 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.32	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.57	D
M_CAP	Pathogenic	0.94	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.67
PrimateAI	Pathogenic	0.94	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.19	B
Vest4		0.24
MutPred		0.16		Gain of stability (P = 0.0826)
MVP		0.48
ClinPred		0.59	D
GERP RS		3.0
PromoterAI		-0.035	Neutral
Varity_R		0.17
gMVP		0.19

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: rs1052714133; hg19: chr17-36508156;