19-53258737-C-G

Variant names:

• chr19-53258737-C-G
• rs200696448
• NM_173856.2:c.362C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_173856.2(VN1R2):​c.362C>G​(p.Pro121Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000837 in 1,613,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000086 (0 hom.)
• Consequence: VN1R2 NM_173856.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.00
• Publications: 1 publications found

Genes affected

VN1R2 (HGNC:19872): (vomeronasal 1 receptor 2) Predicted to enable pheromone receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway and response to pheromone. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09339228).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173856.2. 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
	VN1R2	NM_173856.2	MANE Select	c.362C>G	p.Pro121Arg	missense	Exon 1 of 1	NP_776255.2	Q8NFZ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VN1R2	ENST00000341702.3	TSL:6 MANE Select	c.362C>G	p.Pro121Arg	missense	Exon 1 of 1	ENSP00000351244.2	Q8NFZ6

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152140 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000108 AC: 27 AN: 250768 AF XY: 0.000118

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000855 AC: 125 AN: 1461596 Hom.: 0 Cov.: 32 AF XY: 0.0000839 AC XY: 61 AN XY: 727130

African (AFR) AF: 0.00 AC: 0 AN: 33432

American (AMR) AF: 0.000313 AC: 14 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

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

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5766

European-Non Finnish (NFE) AF: 0.0000800 AC: 89 AN: 1111914

Other (OTH) AF: 0.000116 AC: 7 AN: 60382

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152258 Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4 AN XY: 74460

African (AFR) AF: 0.00 AC: 0 AN: 41552

American (AMR) AF: 0.0000654 AC: 1 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68016

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000158 Hom.: 0

Bravo AF: 0.0000718

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000988 AC: 12

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.2
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0015	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.0065	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		-2.0
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.065
Sift	Benign	0.097	T
Sift4G	Benign	0.21	T
Polyphen		0.82	P
Vest4		0.14
MVP		0.31
MPC		0.24
ClinPred		0.050	T
GERP RS		-2.2
PromoterAI		0.0083	Neutral
Varity_R		0.059
gMVP		0.10
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs200696448; hg19: chr19-53761990;