rs5930932

Positions:

• chrX-136349077-T-A
• chrX-136349077-T-C

Variant summary

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

The NM_153834.4(ADGRG4):​c.5371T>A​(p.Phe1791Ile) 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. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F1791L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., 0 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: ADGRG4 NM_153834.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.794

Genes affected

ADGRG4 (HGNC:18992): (adhesion G protein-coupled receptor G4) This gene encodes a G-protein coupled receptor belonging to a large family of diverse integral membrane proteins that participate in various physiological functions. Members of this superfamily are characterized by a signature 7-transmembrane domain motif. The ligand for this family member is unknown, and it is therefore an orphan receptor. This receptor is known to be expressed in normal enterochromaffin cells and in gastrointestinal neuroendocrine carcinoma cells, and it is therefore considered to be a novel biomarker or target for immunotherapy. [provided by RefSeq, May 2010]

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=0.033104002).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRG4	NM_153834.4	c.5371T>A	p.Phe1791Ile	missense_variant	6/26	ENST00000394143.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRG4	ENST00000394143.6	c.5371T>A	p.Phe1791Ile	missense_variant	6/26	1	NM_153834.4	P1
ADGRG4	ENST00000394141.1	c.4756T>A	p.Phe1586Ile	missense_variant	3/23	1
ADGRG4	ENST00000370652.5	c.5371T>A	p.Phe1791Ile	missense_variant	4/24	5		P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 110051 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 32347 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 110051 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 32347

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.33
DANN	Benign	0.91
DEOGEN2	Benign	0.0067	T;T;.
FATHMM_MKL	Benign	0.015	N
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.033	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.51	N;N;N
REVEL	Benign	0.0080
Sift	Uncertain	0.0090	D;D;D
Sift4G	Benign	0.32	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.093
MutPred		0.16		Loss of catalytic residue at F1791 (P = 0.0345);Loss of catalytic residue at F1791 (P = 0.0345);.;
MVP		0.040
MPC		0.042
ClinPred		0.053	T
GERP RS		-1.8
Varity_R		0.054
gMVP		0.082

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

LitVar

Other links and lift over

dbSNP: rs5930932; hg19: chrX-135431236;