3-120167547-T-G

Variant summary

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

The NM_153002.3(GPR156):c.1930A>C(p.Ser644Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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)
• Consequence: GPR156 NM_153002.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.146

Genes affected

GPR156 (HGNC:20844): (G protein-coupled receptor 156) G protein-coupled receptors (GPCRs) are a large superfamily of cell surface receptors characterized by 7 helical transmembrane domains, together with N-terminal extracellular and C-terminal intracellular domains.[supplied by OMIM, Mar 2008]

LOC105374065 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.050356448).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR156	NM_153002.3	c.1930A>C	p.Ser644Arg	missense_variant	10/10	ENST00000464295.6
LOC105374065	XR_924392.3	n.284-15963T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR156	ENST00000464295.6	c.1930A>C	p.Ser644Arg	missense_variant	10/10	5	NM_153002.3	A2
GPR156	ENST00000461057.1	c.1918A>C	p.Ser640Arg	missense_variant	9/9	1		P4
GPR156	ENST00000495912.5	c.*993A>C		3_prime_UTR_variant, NMD_transcript_variant	4/4	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

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

Mar 28, 2022

The c.1930A>C (p.S644R) alteration is located in exon 9 (coding exon 9) of the GPR156 gene. This alteration results from a A to C substitution at nucleotide position 1930, causing the serine (S) at amino acid position 644 to be replaced by an arginine (R). 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	0.12
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
Cadd	Benign	5.0
Dann	Benign	0.85
DEOGEN2	Benign	0.0012	T;T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.45	T;.;T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.050	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N;N;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.080	N;N;N
REVEL	Benign	0.015
Sift	Benign	0.53	T;T;T
Sift4G	Benign	0.39	T;T;T
Polyphen		0.0030	B;B;.
Vest4		0.050
MutPred		0.18		Gain of MoRF binding (P = 0.0124);Gain of MoRF binding (P = 0.0124);.;
MVP		0.014
MPC		0.27
ClinPred		0.034	T
GERP RS		-2.3
Varity_R		0.055
gMVP		0.15

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: chr3-119886394;