Genetic Variant NM_020633.4:c.979A>G (chr19-57455508-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020633.4(VN1R1):c.979A>G(p.Met327Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

VN1R1
NM_020633.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -4.56

Variant links:

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]

VN1R1 links:

ENSG00000268163 (HGNC:):

ENSG00000268163 links:

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ACMG classification

Classification made for transcript

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=0.040948868).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VN1R1	NM_020633.4 link	c.979A>G	p.Met327Val	missense_variant	Exon 1 of 1	ENST00000321039.5	NP_065684.1	Q9GZP7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
VN1R1	ENST00000321039.5 link	c.979A>G	p.Met327Val	missense_variant	Exon 1 of 1	6	NM_020633.4	ENSP00000322339.3	Q9GZP7
ENSG00000268163	ENST00000596831.1 link	c.347+145A>G		intron_variant	Intron 5 of 5	2		ENSP00000470969.1	M0R036
ENSG00000268163	ENST00000415705.3 link	n.592A>G		non_coding_transcript_exon_variant	Exon 4 of 4	2
ENSG00000268163	ENST00000601945.1 link	n.350A>G		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251434

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135892

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461854

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.979A>G (p.M327V) alteration is located in exon 1 (coding exon 1) of the VN1R1 gene. This alteration results from a A to G substitution at nucleotide position 979, causing the methionine (M) at amino acid position 327 to be replaced by a valine (V). 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

0.071

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.84

DANN

Benign

0.29

DEOGEN2

Benign

0.0017

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.4

FATHMM_MKL

Benign

0.00065

LIST_S2

Benign

0.42

M_CAP

Benign

0.0027

MetaRNN

Benign

0.041

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.2

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.070

REVEL

Benign

0.017

Sift

Benign

0.51

Sift4G

Benign

0.52

Polyphen

0.032

Vest4

0.027

MutPred

0.51

Gain of catalytic residue at M327 (P = 0.0075);

MVP

0.067

MPC

0.035

ClinPred

0.033

GERP RS

-8.2

Varity_R

0.025

gMVP

0.047

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over