chr9-123034637-C-G

Position:

• chr9-123034637-C-G

Variant summary

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

The NM_005294.3(GPR21):​c.71C>G​(p.Thr24Ser) 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. 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: 32)
• Consequence: GPR21 NM_005294.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.65

Genes affected

GPR21 (HGNC:4476): (G protein-coupled receptor 21) This gene encodes a member of the G-protein-coupled receptor 1 family. G-protein coupled receptors are membrane proteins which activate signaling cascades as a response to extracellular stress. The encoded protein activates a Gq signal transduction pathway which mobilizes calcium. [provided by RefSeq, Nov 2012]

RABGAP1 (HGNC:17155): (RAB GTPase activating protein 1) Enables GTPase activator activity and small GTPase binding activity. Involved in regulation of GTPase activity. 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=0.09455916).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR21	NM_005294.3	c.71C>G	p.Thr24Ser	missense_variant	2/2	ENST00000616002.3
RABGAP1	NM_012197.4	c.1794+14178C>G		intron_variant		ENST00000373647.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR21	ENST00000616002.3	c.71C>G	p.Thr24Ser	missense_variant	2/2	1	NM_005294.3	P1
RABGAP1	ENST00000373647.9	c.1794+14178C>G		intron_variant		1	NM_012197.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Jan 19, 2024

The c.71C>G (p.T24S) alteration is located in exon 1 (coding exon 1) of the GPR21 gene. This alteration results from a C to G substitution at nucleotide position 71, causing the threonine (T) at amino acid position 24 to be replaced by a serine (S). 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	0.093
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	15
DANN	Benign	0.86
DEOGEN2	Benign	0.016	.;T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.14
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.23	.;T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.095	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	.;N
MutationTaster	Benign	1.0	D;D;N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.38	.;N
REVEL	Benign	0.098
Sift	Benign	0.51	.;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0060	.;B
Vest4		0.11
MutPred		0.49		Loss of glycosylation at T24 (P = 0.1112);Loss of glycosylation at T24 (P = 0.1112);
MVP		0.16
MPC		0.18
ClinPred		0.51	D
GERP RS		4.6
Varity_R		0.061
gMVP		0.085

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: chr9-125796916;