19-57455642-A-C

Position:

• chr19-57455642-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_020633.4(VN1R1):​c.845T>G​(p.Phe282Cys) 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 pathogenic outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: VN1R1 NM_020633.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.05

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.862

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VN1R1	NM_020633.4	c.845T>G	p.Phe282Cys	missense_variant	1/1	ENST00000321039.5	NP_065684.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VN1R1	ENST00000321039.5	c.845T>G	p.Phe282Cys	missense_variant	1/1	6	NM_020633.4	ENSP00000322339.3
ENSG00000268163	ENST00000596831.1	c.347+11T>G		intron_variant		2		ENSP00000470969.1
ENSG00000268163	ENST00000415705.3	n.458T>G		non_coding_transcript_exon_variant	4/4	2
ENSG00000268163	ENST00000601945.1	n.216T>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 20, 2024

The c.845T>G (p.F282C) alteration is located in exon 1 (coding exon 1) of the VN1R1 gene. This alteration results from a T to G substitution at nucleotide position 845, causing the phenylalanine (F) at amino acid position 282 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.024	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.021	T
MetaRNN	Pathogenic	0.86	D
MetaSVM	Benign	-0.80	T
MutationAssessor	Pathogenic	3.6	H
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-6.8	D
REVEL	Benign	0.14
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.017	D
Polyphen		1.0	D
Vest4		0.39
MutPred		0.82		Loss of stability (P = 0.024);
MVP		0.47
MPC		0.28
ClinPred		0.69	D
GERP RS		0.56
Varity_R		0.45
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-57967010;