chrX-136323051-C-T

Position:

• chrX-136323051-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_153834.4(ADGRG4):​c.344C>T​(p.Ala115Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,097,681 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.000012 (0 hom. 5 hem.)
• Consequence: ADGRG4 NM_153834.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.299

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 Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.032846987).
• BS2: High Hemizygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRG4	NM_153834.4	c.344C>T	p.Ala115Val	missense_variant	5/26	ENST00000394143.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRG4	ENST00000394143.6	c.344C>T	p.Ala115Val	missense_variant	5/26	1	NM_153834.4	P1
ADGRG4	ENST00000394141.1	c.70+14204C>T		intron_variant		1
ADGRG4	ENST00000370652.5	c.344C>T	p.Ala115Val	missense_variant	3/24	5		P1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD3 exomes AF: 0.0000273 AC: 5 AN: 183152 Hom.: 0 AF XY: 0.0000295 AC XY: 2 AN XY: 67684

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000361

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000118 AC: 13 AN: 1097681 Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 5 AN XY: 363043

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000430

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

Bravo AF: 0.0000113

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	5.7
DANN	Benign	0.92
DEOGEN2	Benign	0.0039	T;T
FATHMM_MKL	Benign	0.021	N
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.033	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.47	N;N
REVEL	Benign	0.018
Sift	Benign	0.064	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.059	B;B
Vest4		0.23
MutPred		0.40		Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);
MVP		0.16
MPC		0.036
ClinPred		0.017	T
GERP RS		-3.0
Varity_R		0.046
gMVP		0.29

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: rs748048833; hg19: chrX-135405210;