NM_020633.4:c.277G>T

Variant names:

• chr19-57456210-C-A
• rs749270907
• NM_020633.4:c.277G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020633.4(VN1R1):​c.277G>T​(p.Ala93Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/22 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. A93T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: VN1R1 NM_020633.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.497
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.277G>T	p.Ala93Ser	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.277G>T	p.Ala93Ser	missense	Exon 1 of 1	ENSP00000322339.3	Q9GZP7
	ENSG00000268163	ENST00000596831.1	TSL:2	c.200-28G>T		intron	N/A	ENSP00000470969.1	M0R036
	ENSG00000268163	ENST00000601945.1	TSL:2	n.30G>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461888 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727244

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	T
Eigen	Benign	0.13
Eigen_PC	Benign	-0.016
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0047	T
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.50
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.21
Sift	Benign	0.052	T
Sift4G	Uncertain	0.035	D
Polyphen		1.0	D
Vest4		0.17
MutPred		0.73		Loss of stability (P = 0.5212)
MVP		0.32
MPC		0.22
ClinPred		0.94	D
GERP RS		4.2
Varity_R		0.25
gMVP		0.091
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs749270907; hg19: chr19-57967578;