Genetic Variant VIP:p.Ser91Gly (chr6-152755309-A-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_003381.4(VIP):c.271A>G(p.Ser91Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000332 in 1,596,324 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

VIP
NM_003381.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.90

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:54374): (long intergenic non-protein coding RNA 2840)

LINC02840 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VIP	NM_003381.4 link	c.271A>G	p.Ser91Gly	missense_variant	Exon 4 of 7	ENST00000367244.8	NP_003372.1	P01282-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
VIP	ENST00000367244.8 link	c.271A>G	p.Ser91Gly	missense_variant	Exon 4 of 7	1	NM_003381.4	ENSP00000356213.3	P01282-1
VIP	ENST00000367243.7 link	c.271A>G	p.Ser91Gly	missense_variant	Exon 4 of 7	1		ENSP00000356212.3	P01282-2
VIP	ENST00000431366.1 link	c.118A>G	p.Ser40Gly	missense_variant	Exon 2 of 5	3		ENSP00000410356.1	H0Y763
LINC02840	ENST00000666093.1 link	n.4012T>C		non_coding_transcript_exon_variant	Exon 5 of 5

Frequencies

GnomAD3 genomes

AF:

0.000191

AC:

AN:

151936

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000165

AC:

AN:

242794

Hom.:

AF XY:

0.00000761

AC XY:

AN XY:

131430

show subpopulations

Gnomad AFR exome

AF:

0.000191

Gnomad AMR exome

AF:

0.0000307

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:

0.00

GnomAD4 exome

AF:

0.0000166

AC:

AN:

1444388

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

717918

show subpopulations

Gnomad4 AFR exome

AF:

0.000608

Gnomad4 AMR exome

AF:

0.0000232

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:

0.00000272

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000191

AC:

AN:

151936

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74228

show subpopulations

Gnomad4 AFR

AF:

0.000676

Gnomad4 AMR

AF:

0.0000657

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000988

Hom.:

Bravo

AF:

0.000242

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

Jun 17, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.271A>G (p.S91G) alteration is located in exon 4 (coding exon 3) of the VIP gene. This alteration results from a A to G substitution at nucleotide position 271, causing the serine (S) at amino acid position 91 to be replaced by a glycine (G). 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

0.36

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.51

D;.

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

D;D

M_CAP

Benign

0.042

MetaRNN

Uncertain

0.50

D;D

MetaSVM

Benign

-0.48

MutationAssessor

Pathogenic

3.2

M;M

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-2.5

D;D

REVEL

Uncertain

0.38

Sift

Benign

0.12

T;T

Sift4G

Benign

0.41

T;T

Polyphen

0.93

P;D

Vest4

0.56

MVP

0.23

MPC

0.45

ClinPred

0.92

GERP RS

4.9

Varity_R

0.28

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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