17-38352957-C-T

Variant names:

• chr17-38352957-C-T
• NM_014598.4:c.905C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014598.4(SOCS7):​c.905C>T​(p.Ser302Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,455,532 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. 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. S302C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SOCS7 NM_014598.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.66

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10370964).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOCS7	NM_014598.4	c.905C>T	p.Ser302Phe	missense_variant	Exon 1 of 10	ENST00000612932.6	NP_055413.2
SOCS7	XM_017024551.2	c.905C>T	p.Ser302Phe	missense_variant	Exon 1 of 9		XP_016880040.1
SOCS7	XM_017024552.2	c.905C>T	p.Ser302Phe	missense_variant	Exon 1 of 8		XP_016880041.1
SOCS7	XR_007065295.1	n.1114C>T		non_coding_transcript_exon_variant	Exon 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOCS7	ENST00000612932.6	c.905C>T	p.Ser302Phe	missense_variant	Exon 1 of 10	1	NM_014598.4	ENSP00000482229.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1455532 Hom.: 0 Cov.: 33 AF XY: 0.00000276 AC XY: 2 AN XY: 723448

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: 0.0000118

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Benign	0.95
DEOGEN2	Uncertain	0.46	.;T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.63	D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	.;L
PrimateAI	Uncertain	0.69	T
Sift4G	Benign	0.11	T;D
Polyphen		0.0	.;B
Vest4		0.15
MutPred		0.18		Loss of phosphorylation at S238 (P = 0.0055);Loss of phosphorylation at S238 (P = 0.0055);
MVP		0.54
ClinPred		0.80	D
GERP RS		3.3
Varity_R		0.17
gMVP		0.55

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-36508840;