Variant chr1-115651454-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_138959.3(VANGL1):c.41C>T(p.Ser14Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,613,948 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

VANGL1
NM_138959.3 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 4.65

Variant links:

Genes affected

VANGL1 (HGNC:15512): (VANGL planar cell polarity protein 1) This gene encodes a member of the tretraspanin family. The encoded protein may be involved in mediating intestinal trefoil factor induced wound healing in the intestinal mucosa. Mutations in this gene are associated with neural tube defects. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2010]

VANGL1 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/exons	MANE
VANGL1	NM_138959.3 linkuse as main transcript	c.41C>T	p.Ser14Leu	missense_variant	2/8	ENST00000355485.7
VANGL1	NM_001172412.2 linkuse as main transcript	c.41C>T	p.Ser14Leu	missense_variant	2/8
VANGL1	NM_001172411.2 linkuse as main transcript	c.41C>T	p.Ser14Leu	missense_variant	2/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VANGL1	ENST00000355485.7 linkuse as main transcript	c.41C>T	p.Ser14Leu	missense_variant	2/8	1	NM_138959.3	P3	Q8TAA9-1
VANGL1	ENST00000310260.7 linkuse as main transcript	c.41C>T	p.Ser14Leu	missense_variant	2/8	1		P3	Q8TAA9-1
VANGL1	ENST00000369509.1 linkuse as main transcript	c.41C>T	p.Ser14Leu	missense_variant	1/7	1		P3	Q8TAA9-1
VANGL1	ENST00000369510.8 linkuse as main transcript	c.41C>T	p.Ser14Leu	missense_variant	2/8	1		A1	Q8TAA9-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461788

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727202

show subpopulations

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Keratoconus

Uncertain:1

Uncertain significance, no assertion criteria provided

research

Institute of Human Genetics, Polish Academy of Sciences

Feb 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.63

BayesDel_addAF

Uncertain

0.069

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.45

T;.;T;T

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Uncertain

0.97

LIST_S2

Pathogenic

0.99

D;D;.;.

M_CAP

Uncertain

0.15

MetaRNN

Uncertain

0.44

T;T;T;T

MetaSVM

Uncertain

0.31

MutationAssessor

Benign

1.9

L;L;L;L

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-3.5

D;D;D;D

REVEL

Uncertain

0.42

Sift

Uncertain

0.0050

D;D;D;D

Sift4G

Uncertain

0.0060

D;D;D;D

Polyphen

1.0

D;D;D;D

Vest4

0.61

MutPred

0.21

Loss of phosphorylation at S14 (P = 0.0091);Loss of phosphorylation at S14 (P = 0.0091);Loss of phosphorylation at S14 (P = 0.0091);Loss of phosphorylation at S14 (P = 0.0091);

MVP

0.36

MPC

0.52

ClinPred

0.95

GERP RS

4.9

Varity_R

0.44

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.23

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.23

Position offset: 30

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