1-9111302-G-T

Position:

• chr1-9111302-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_024980.5(GPR157):​c.571C>A​(p.Leu191Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GPR157 NM_024980.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.99

Genes affected

GPR157 (HGNC:23687): (G protein-coupled receptor 157) Predicted to enable G protein-coupled receptor activity. Predicted to be involved in positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway and radial glial cell differentiation. Predicted to be located in ciliary membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.89

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR157	NM_024980.5	c.571C>A	p.Leu191Met	missense_variant	2/4	ENST00000377411.5
GPR157	XM_005263496.6	c.571C>A	p.Leu191Met	missense_variant	2/4
GPR157	XM_005263497.6	c.571C>A	p.Leu191Met	missense_variant	2/3
GPR157	XR_007063977.1	n.646C>A		non_coding_transcript_exon_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR157	ENST00000377411.5	c.571C>A	p.Leu191Met	missense_variant	2/4	1	NM_024980.5	P1
GPR157	ENST00000465853.1	c.70C>A	p.Leu24Met	missense_variant	1/2	5
GPR157	ENST00000466131.1	n.325C>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Nov 03, 2023

The c.571C>A (p.L191M) alteration is located in exon 2 (coding exon 2) of the GPR157 gene. This alteration results from a C to A substitution at nucleotide position 571, causing the leucine (L) at amino acid position 191 to be replaced by a methionine (M). 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	0.15
BayesDel_addAF	Benign	-0.0072	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.033	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.7	M
MutationTaster	Benign	1.0	D;N
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.27
Sift	Benign	0.075	T
Sift4G	Uncertain	0.027	D
Polyphen		1.0	D
Vest4		0.69
MutPred		0.75		Gain of MoRF binding (P = 0.0609);
MVP		0.58
MPC		0.44
ClinPred		0.80	D
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.78

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: chr1-9171361;