19-57455980-G-T

Variant names:

• chr19-57455980-G-T
• NM_020633.4:c.507C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020633.4(VN1R1):​c.507C>A​(p.Asp169Glu) 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. 15/21 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: 0.160

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.066122115).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VN1R1	NM_020633.4	c.507C>A	p.Asp169Glu	missense_variant	Exon 1 of 1	ENST00000321039.5	NP_065684.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VN1R1	ENST00000321039.5	c.507C>A	p.Asp169Glu	missense_variant	Exon 1 of 1	6	NM_020633.4	ENSP00000322339.3
ENSG00000268163	ENST00000596831.1	c.256+146C>A		intron_variant	Intron 4 of 5	2		ENSP00000470969.1
ENSG00000268163	ENST00000415705.3	n.356+146C>A		intron_variant	Intron 3 of 3	2
ENSG00000268163	ENST00000601945.1	n.114+146C>A		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 06, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.507C>A (p.D169E) alteration is located in exon 1 (coding exon 1) of the VN1R1 gene. This alteration results from a C to A substitution at nucleotide position 507, causing the aspartic acid (D) at amino acid position 169 to be replaced by a glutamic acid (E). 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	0.17
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	12
DANN	Benign	0.79
DEOGEN2	Benign	0.0046	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.030	N
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.81	L
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.13
Sift	Uncertain	0.014	D
Sift4G	Benign	0.39	T
Polyphen		0.19	B
Vest4		0.041
MutPred		0.57		Loss of MoRF binding (P = 0.2136);
MVP		0.067
MPC		0.034
ClinPred		0.099	T
GERP RS		-8.5
Varity_R		0.088
gMVP		0.13

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-57967348;