3-42502788-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004624.4(VIPR1):c.53C>T(p.Ala18Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000884 in 1,131,500 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.8e-7 (0 hom.)
• Consequence: VIPR1 NM_004624.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.349

Genes affected

VIPR1 (HGNC:12694): (vasoactive intestinal peptide receptor 1) This gene encodes a receptor for vasoactive intestinal peptide, a small neuropeptide. Vasoactive intestinal peptide is involved in smooth muscle relaxation, exocrine and endocrine secretion, and water and ion flux in lung and intestinal epithelia. Its actions are effected through integral membrane receptors associated with a guanine nucleotide binding protein which activates adenylate cyclase. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1756444).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VIPR1	NM_004624.4	c.53C>T	p.Ala18Val	missense_variant	1/13	ENST00000325123.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VIPR1	ENST00000325123.5	c.53C>T	p.Ala18Val	missense_variant	1/13	1	NM_004624.4	P4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.84e-7 AC: 1 AN: 1131500 Hom.: 0 Cov.: 31 AF XY: 0.00000184 AC XY: 1 AN XY: 542942

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: 0.00000105

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Feb 13, 2024

The c.53C>T (p.A18V) alteration is located in exon 1 (coding exon 1) of the VIPR1 gene. This alteration results from a C to T substitution at nucleotide position 53, causing the alanine (A) at amino acid position 18 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	0.12
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
Cadd	Benign	18
Dann	Benign	0.97
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.56	T;T
M_CAP	Pathogenic	0.35	D
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D;D;N
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.27	N;N
REVEL	Benign	0.064
Sift	Benign	0.086	T;T
Sift4G	Benign	0.17	T;T
Polyphen		0.031	.;B
Vest4		0.21
MutPred		0.49		Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);
MVP		0.30
MPC		0.085
ClinPred		0.96	D
GERP RS		2.3
Varity_R		0.063
gMVP		0.31

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: chr3-42544280;