chr17-38352429-C-T

Variant names:

• chr17-38352429-C-T
• rs1025581444
• NM_014598.4:c.377C>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.377C>T​(p.Ala126Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000767 in 1,303,346 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: 7.7e-7 (0 hom.)
• Consequence: SOCS7 NM_014598.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.263
• 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=0.17402756).

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.377C>T	p.Ala126Val	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.377C>T	p.Ala126Val	missense	Exon 1 of 10	ENSP00000482229.2	A0A5F9YLF9
	SOCS7	ENST00000665913.1		c.185C>T	p.Ala62Val	missense	Exon 1 of 10	ENSP00000499750.1	O14512-1
	SOCS7	ENST00000613678.5	TSL:5	c.200C>T	p.Ala67Val	missense	Exon 1 of 9	ENSP00000484381.2	A0A087X1Q5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.67e-7 AC: 1 AN: 1303346 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 635652

African (AFR) AF: 0.00 AC: 0 AN: 26974

American (AMR) AF: 0.00 AC: 0 AN: 20656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18936

East Asian (EAS) AF: 0.00 AC: 0 AN: 33820

South Asian (SAS) AF: 0.00 AC: 0 AN: 64750

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39634

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4348

European-Non Finnish (NFE) AF: 9.61e-7 AC: 1 AN: 1040432

Other (OTH) AF: 0.00 AC: 0 AN: 53796

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

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	0.22
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.093	N
M_CAP	Pathogenic	0.90	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.26
PrimateAI	Pathogenic	0.92	D
Sift4G	Benign	0.28	T
Polyphen		0.079	B
Vest4		0.25
MutPred		0.19		Loss of disorder (P = 0.2567)
MVP		0.37
ClinPred		0.91	D
GERP RS		2.4
PromoterAI		-0.0077	Neutral
Varity_R		0.085
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: rs1025581444; hg19: chr17-36508312;