chr17-7313416-A-G

Position:

• chr17-7313416-A-G

Variant summary

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

The NM_004489.5(GPS2):​c.688T>C​(p.Tyr230His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPS2 NM_004489.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.69

Genes affected

GPS2 (HGNC:4550): (G protein pathway suppressor 2) This gene encodes a protein involved in G protein-mitogen-activated protein kinase (MAPK) signaling cascades. When overexpressed in mammalian cells, this gene could potently suppress a RAS- and MAPK-mediated signal and interfere with JNK activity, suggesting that the function of this gene may be signal repression. The encoded protein is an integral subunit of the NCOR1-HDAC3 (nuclear receptor corepressor 1-histone deacetylase 3) complex, and it was shown that the complex inhibits JNK activation through this subunit and thus could potentially provide an alternative mechanism for hormone-mediated antagonism of AP1 (activator protein 1) function. [provided by RefSeq, Jul 2008]

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=0.21565318).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPS2	NM_004489.5	c.688T>C	p.Tyr230His	missense_variant	8/11	ENST00000380728.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPS2	ENST00000380728.7	c.688T>C	p.Tyr230His	missense_variant	8/11	1	NM_004489.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 25, 2022

The c.688T>C (p.Y230H) alteration is located in exon 8 (coding exon 7) of the GPS2 gene. This alteration results from a T to C substitution at nucleotide position 688, causing the tyrosine (Y) at amino acid position 230 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T;T;T;T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.0073
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.84	T;.;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.22	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.97	.;L;L;.
MutationTaster	Benign	0.96	D;D;D
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-0.78	.;N;N;.
REVEL	Benign	0.24
Sift	Pathogenic	0.0	.;D;D;.
Sift4G	Benign	0.13	T;T;T;.
Polyphen		0.026	.;B;B;.
Vest4		0.64, 0.63
MutPred		0.25		.;Loss of phosphorylation at Y230 (P = 0.0158);Loss of phosphorylation at Y230 (P = 0.0158);Loss of phosphorylation at Y230 (P = 0.0158);
MVP		0.94
ClinPred		0.68	D
GERP RS		3.6
Varity_R		0.32
gMVP		0.54

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: chr17-7216735;