19-57456270-T-G

Variant names:

• chr19-57456270-T-G
• rs144835279
• NM_020633.4:c.217A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020633.4(VN1R1):​c.217A>C​(p.Ile73Leu) 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. 16/22 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. I73V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: VN1R1 NM_020633.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.443
• Publications: 0 publications found

Genes affected

VN1R1 (HGNC:13548): (vomeronasal 1 receptor 1) Pheromones are chemical signals that elicit specific behavioral responses and physiologic alterations in recipients of the same species. The protein encoded by this gene is similar to pheromone receptors and is primarily localized to the olfactory mucosa. An alternate splice variant of this gene is thought to exist, but its full length nature has not been determined. [provided by RefSeq, Jul 2008]

ENSG00000268163 (HGNC:):

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048214287).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020633.4. 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
	VN1R1	NM_020633.4	MANE Select	c.217A>C	p.Ile73Leu	missense	Exon 1 of 1	NP_065684.1	Q9GZP7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VN1R1	ENST00000321039.5	TSL:6 MANE Select	c.217A>C	p.Ile73Leu	missense	Exon 1 of 1	ENSP00000322339.3	Q9GZP7
	ENSG00000268163	ENST00000596831.1	TSL:2	c.200-88A>C		intron	N/A	ENSP00000470969.1	M0R036
	ENSG00000268163	ENST00000415705.3	TSL:2	n.300-88A>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.30
DANN	Benign	0.29
DEOGEN2	Benign	0.0040	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.41	N
PhyloP100		-0.44
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.060	N
REVEL	Benign	0.034
Sift	Benign	1.0	T
Sift4G	Benign	0.71	T
Polyphen		0.024	B
Vest4		0.10
MutPred		0.59		Loss of catalytic residue at I73 (P = 0.0809)
MVP		0.076
MPC		0.036
ClinPred		0.031	T
GERP RS		-2.2
Varity_R		0.059
gMVP		0.15
Mutation Taster		=99/1	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: rs144835279; hg19: chr19-57967638;