Variant 6-152755352-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_003381.4(VIP):c.314C>A(p.Ser105Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000699 in 1,430,364 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000070 ( 0 hom. )

Consequence

VIP
NM_003381.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.52

Variant links:

Genes affected

VIP (HGNC:12693): (vasoactive intestinal peptide) The protein encoded by this gene belongs to the glucagon family. It stimulates myocardial contractility, causes vasodilation, increases glycogenolysis, lowers arterial blood pressure and relaxes the smooth muscle of trachea, stomach and gall bladder. The protein also acts as an antimicrobial peptide with antibacterial and antifungal activity. Alternative splicing occurs at this locus and two transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Nov 2014]

VIP links:

LINC02840 (HGNC:):

LINC02840 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.823

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VIP	NM_003381.4 linkuse as main transcript	c.314C>A	p.Ser105Tyr	missense_variant	4/7	ENST00000367244.8	NP_003372.1	P01282-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
VIP	ENST00000367244.8 linkuse as main transcript	c.314C>A	p.Ser105Tyr	missense_variant	4/7	1	NM_003381.4	ENSP00000356213.3	P01282-1
VIP	ENST00000367243.7 linkuse as main transcript	c.314C>A	p.Ser105Tyr	missense_variant	4/7	1		ENSP00000356212.3	P01282-2
VIP	ENST00000431366.1 linkuse as main transcript	c.161C>A	p.Ser54Tyr	missense_variant	2/5	3		ENSP00000410356.1	H0Y763
LINC02840	ENST00000666093.1 linkuse as main transcript	n.3969G>T		non_coding_transcript_exon_variant	5/5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000255

AC:

AN:

234940

Hom.:

AF XY:

0.00000784

AC XY:

AN XY:

127516

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000163

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:

0.00

Gnomad OTH exome

AF:

0.000181

GnomAD4 exome

AF:

0.00000699

AC:

AN:

1430364

Hom.:

Cov.:

AF XY:

0.00000563

AC XY:

AN XY:

710652

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000168

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:

0.00000182

Gnomad4 OTH exome

AF:

0.0000170

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 27, 2024

The c.314C>A (p.S105Y) alteration is located in exon 4 (coding exon 3) of the VIP gene. This alteration results from a C to A substitution at nucleotide position 314, causing the serine (S) at amino acid position 105 to be replaced by a tyrosine (Y). 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

Uncertain

0.35

BayesDel_addAF

Uncertain

0.013

BayesDel_noAF

Uncertain

0.050

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.58

D;.

Eigen

Pathogenic

0.70

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

D;D

M_CAP

Benign

0.059

MetaRNN

Pathogenic

0.82

D;D

MetaSVM

Benign

-0.78

MutationAssessor

Pathogenic

3.2

M;M

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-5.4

D;D

REVEL

Uncertain

0.30

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;D

Vest4

0.87

MutPred

0.49

Loss of disorder (P = 0.0103);Loss of disorder (P = 0.0103);

MVP

0.14

MPC

0.64

ClinPred

0.98

GERP RS

4.2

Varity_R

0.76

gMVP

0.44

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

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