3-42519233-G-T

Variant names:

• chr3-42519233-G-T
• NM_004624.4:c.195G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004624.4(VIPR1):​c.195G>T​(p.Lys65Asn) 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. 15/22 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)
• Consequence: VIPR1 NM_004624.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.126
• Publications: 0 publications found

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]

VIPR1-AS1 (HGNC:40610): (VIPR1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25488228).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004624.4. 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
	VIPR1	NM_004624.4	MANE Select	c.195G>T	p.Lys65Asn	missense	Exon 3 of 13	NP_004615.2
	VIPR1	NM_001251885.2		c.114G>T	p.Lys38Asn	missense	Exon 3 of 13	NP_001238814.1	B4DNY6
	VIPR1	NM_001251882.2		c.72G>T	p.Lys24Asn	missense	Exon 4 of 14	NP_001238811.1	P32241-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VIPR1	ENST00000325123.5	TSL:1 MANE Select	c.195G>T	p.Lys65Asn	missense	Exon 3 of 13	ENSP00000327246.4	P32241-1
	VIPR1	ENST00000883021.1		c.195G>T	p.Lys65Asn	missense	Exon 3 of 13	ENSP00000553080.1
	VIPR1	ENST00000883016.1		c.195G>T	p.Lys65Asn	missense	Exon 3 of 13	ENSP00000553075.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Benign	0.88
DEOGEN2	Benign	0.025	T
Eigen	Benign	0.030
Eigen_PC	Benign	0.056
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.13
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	0.59	N
REVEL	Benign	0.13
Sift	Uncertain	0.010	D
Sift4G	Benign	0.14	T
Polyphen		0.74	P
Vest4		0.34
MutPred		0.63		Loss of ubiquitination at K65 (P = 0.0255)
MVP		0.66
MPC		0.30
ClinPred		0.64	D
GERP RS		2.8
Varity_R		0.092
gMVP		0.73
Mutation Taster		=76/24	polymorphism

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

Other links and lift over

hg19: chr3-42560725;