6-152752226-A-T

Position:

• chr6-152752226-A-T

Variant summary

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

The NM_003381.4(VIP):​c.49A>T​(p.Ser17Cys) 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. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: VIP NM_003381.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.42

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]

ACMG classification

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/exons	MANE	Protein	UniProt
VIP	NM_003381.4	c.49A>T	p.Ser17Cys	missense_variant	2/7	ENST00000367244.8	NP_003372.1
VIP	NM_194435.3	c.49A>T	p.Ser17Cys	missense_variant	2/7		NP_919416.1
VIP	XM_006715562.5	c.49A>T	p.Ser17Cys	missense_variant	2/7		XP_006715625.1
VIP	XM_005267135.4	c.49A>T	p.Ser17Cys	missense_variant	2/7		XP_005267192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VIP	ENST00000367244.8	c.49A>T	p.Ser17Cys	missense_variant	2/7	1	NM_003381.4	ENSP00000356213.3
VIP	ENST00000367243.7	c.49A>T	p.Ser17Cys	missense_variant	2/7	1		ENSP00000356212.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

See cases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

New York Genome Center

Jun 12, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	19
DANN	Benign	0.36
DEOGEN2	Uncertain	0.52	D;.
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.64
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.56	T;T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;L
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.74	N;N
REVEL	Benign	0.16
Sift	Benign	0.18	T;T
Sift4G	Benign	0.18	T;T
Polyphen		0.062	B;B
Vest4		0.43
MutPred		0.47		Gain of catalytic residue at S17 (P = 0.145);Gain of catalytic residue at S17 (P = 0.145);
MVP		0.040
MPC		0.11
ClinPred		0.15	T
GERP RS		3.2
Varity_R		0.063
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.66		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.66		Position offset: 18

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: chr6-153073361;