17-38352288-T-C

Position:

• chr17-38352288-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_014598.4(SOCS7):​c.236T>C​(p.Val79Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000749 in 1,335,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: SOCS7 NM_014598.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0900

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.038355082).
• BP6: Variant 17-38352288-T-C is Benign according to our data. Variant chr17-38352288-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2569531.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOCS7	NM_014598.4	c.236T>C	p.Val79Ala	missense_variant	1/10	ENST00000612932.6	NP_055413.2
SOCS7	XM_017024551.2	c.236T>C	p.Val79Ala	missense_variant	1/9		XP_016880040.1
SOCS7	XM_017024552.2	c.236T>C	p.Val79Ala	missense_variant	1/8		XP_016880041.1
SOCS7	XR_007065295.1	n.445T>C		non_coding_transcript_exon_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOCS7	ENST00000612932.6	c.236T>C	p.Val79Ala	missense_variant	1/10	1	NM_014598.4	ENSP00000482229.2
SOCS7	ENST00000665913.1	c.44T>C	p.Val15Ala	missense_variant	1/10			ENSP00000499750.1
SOCS7	ENST00000613678.5	c.59T>C	p.Val20Ala	missense_variant	1/9	5		ENSP00000484381.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.49e-7 AC: 1 AN: 1335866 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 660528

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.42e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	15
DANN	Benign	0.82
DEOGEN2	Benign	0.18	.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.014	N
M_CAP	Pathogenic	0.35	D
MetaRNN	Benign	0.038	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	.;N
PrimateAI	Pathogenic	0.92	D
Sift4G	Benign	0.92	T;T
Polyphen		0.0	.;B
Vest4		0.061
MutPred		0.077		Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);
MVP		0.068
ClinPred		0.092	T
GERP RS		1.3
Varity_R		0.030
gMVP		0.11

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

LitVar

Other links and lift over

dbSNP: rs1418886486; hg19: chr17-36508171;