chr17-38352450-C-T

Variant names:

• chr17-38352450-C-T
• NM_014598.4:c.398C>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.398C>T​(p.Ala133Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000229 in 1,308,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 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: 0.0000023 (0 hom.)
• Consequence: SOCS7 NM_014598.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.121
• 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=0.13536197).

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.398C>T	p.Ala133Val	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.398C>T	p.Ala133Val	missense	Exon 1 of 10	ENSP00000482229.2	A0A5F9YLF9
	SOCS7	ENST00000665913.1		c.206C>T	p.Ala69Val	missense	Exon 1 of 10	ENSP00000499750.1	O14512-1
	SOCS7	ENST00000613678.5	TSL:5	c.221C>T	p.Ala74Val	missense	Exon 1 of 9	ENSP00000484381.2	A0A087X1Q5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000229 AC: 3 AN: 1308536 Hom.: 0 Cov.: 31 AF XY: 0.00000313 AC XY: 2 AN XY: 638042

African (AFR) AF: 0.00 AC: 0 AN: 27242

American (AMR) AF: 0.00 AC: 0 AN: 21332

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19160

East Asian (EAS) AF: 0.00 AC: 0 AN: 33896

South Asian (SAS) AF: 0.00 AC: 0 AN: 65824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42070

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4512

European-Non Finnish (NFE) AF: 0.00000288 AC: 3 AN: 1040550

Other (OTH) AF: 0.00 AC: 0 AN: 53950

GnomAD4 genome Cov.: 33

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	0.10
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	18
DANN	Benign	0.88
DEOGEN2	Benign	0.21	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.029	N
M_CAP	Pathogenic	0.76	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.12
PrimateAI	Pathogenic	0.88	D
Sift4G	Benign	0.36	T
Polyphen		0.0020	B
Vest4		0.13
MutPred		0.10		Loss of relative solvent accessibility (P = 0.0186)
MVP		0.22
ClinPred		0.86	D
GERP RS		0.031
PromoterAI		0.021	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Varity_R		0.047
gMVP		0.21
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

hg19: chr17-36508333;