19-50770794-T-G

Variant names:

• chr19-50770794-T-G
• rs149687485
• NM_001506.2:c.194T>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001506.2(GPR32):​c.194T>G​(p.Leu65Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. L65P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GPR32 NM_001506.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.97
• Publications: 1 publications found

Genes affected

GPR32 (HGNC:4487): (G protein-coupled receptor 32) This gene is intronless and encodes a member of the G-protein coupled receptor 1 family. The encoded protein binds to resolvin D1 and lipoxin A4 and has been linked to pulmonary inflammation. A related pseudogene has been identified on chromosome 19. [provided by RefSeq, Nov 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.912

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001506.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR32	NM_001506.2	MANE Select	c.194T>G	p.Leu65Arg	missense	Exon 1 of 1	NP_001497.1	O75388

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR32	ENST00000270590.4	TSL:6 MANE Select	c.194T>G	p.Leu65Arg	missense	Exon 1 of 1	ENSP00000270590.3	O75388

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251392 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 6.84e-7 AC: 1 AN: 1461850 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727236

African (AFR) AF: 0.00 AC: 0 AN: 33450

American (AMR) AF: 0.0000224 AC: 1 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112002

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.13
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T
Eigen	Benign	0.10
Eigen_PC	Benign	0.036
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.40	T
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.91	D
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		7.0
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Uncertain	0.50
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.012	D
Polyphen		0.71	P
Vest4		0.57
MutPred		0.81		Gain of MoRF binding (P = 0.0069)
MVP		0.86
MPC		1.2
ClinPred		0.99	D
GERP RS		2.6
PromoterAI		-0.011	Neutral
Varity_R		0.74
gMVP		0.56
Mutation Taster		=54/46	polymorphism

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

Other links and lift over

dbSNP: rs149687485; hg19: chr19-51274051;