19-50770794-T-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001506.2(GPR32):​c.194T>A​(p.Leu65Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000014 (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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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>A	p.Leu65Gln	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>A	p.Leu65Gln	missense	Exon 1 of 1	ENSP00000270590.3	O75388

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251392 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461850 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727236

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

American (AMR) AF: 0.00 AC: 0 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: 0.0000187 AC: 1 AN: 53420

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 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	0.79
BayesDel_addAF	Uncertain	0.042	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.35	T
M_CAP	Uncertain	0.088	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.34	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		7.0
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Uncertain	0.40
Sift	Uncertain	0.021	D
Sift4G	Benign	0.072	T
Polyphen		0.063	B
Vest4		0.53
MutPred		0.60		Loss of sheet (P = 0.0817)
MVP		0.76
MPC		0.60
ClinPred		0.87	D
GERP RS		2.6
PromoterAI		-0.022	Neutral
Varity_R		0.50
gMVP		0.34
Mutation Taster		=65/35	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;