Variant 1-115659765-G-A 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.196G>A(p.Glu66Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

VANGL1
NM_138959.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.84

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:

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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
VANGL1	NM_138959.3 link	c.196G>A	p.Glu66Lys	missense_variant	Exon 3 of 8	ENST00000355485.7	NP_620409.1	Q8TAA9-1A0A024R0E3
VANGL1	NM_001172412.2 link	c.196G>A	p.Glu66Lys	missense_variant	Exon 3 of 8		NP_001165883.1	Q8TAA9-1A0A024R0E3
VANGL1	NM_001172411.2 link	c.196G>A	p.Glu66Lys	missense_variant, splice_region_variant	Exon 3 of 8		NP_001165882.1	Q8TAA9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
VANGL1	ENST00000355485.7 link	c.196G>A	p.Glu66Lys	missense_variant	Exon 3 of 8	1	NM_138959.3	ENSP00000347672.2	Q8TAA9-1
VANGL1	ENST00000310260.7 link	c.196G>A	p.Glu66Lys	missense_variant	Exon 3 of 8	1		ENSP00000310800.3	Q8TAA9-1
VANGL1	ENST00000369509.1 link	c.196G>A	p.Glu66Lys	missense_variant	Exon 2 of 7	1		ENSP00000358522.1	Q8TAA9-1
VANGL1	ENST00000369510.8 link	c.196G>A	p.Glu66Lys	missense_variant, splice_region_variant	Exon 3 of 8	1		ENSP00000358523.3	Q8TAA9-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

May 04, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.196G>A (p.E66K) alteration is located in exon 3 (coding exon 2) of the VANGL1 gene. This alteration results from a G to A substitution at nucleotide position 196, causing the glutamic acid (E) at amino acid position 66 to be replaced by a lysine (K). 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

Benign

0.19

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

T;.;T;T

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

D;T;.;.

M_CAP

Benign

0.044

MetaRNN

Benign

0.39

T;T;T;T

MetaSVM

Benign

-0.39

MutationAssessor

Benign

1.4

L;L;L;L

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-2.4

N;N;N;N

REVEL

Uncertain

0.50

Sift

Uncertain

0.020

D;D;D;D

Sift4G

Benign

0.17

T;T;T;T

Polyphen

0.67

P;B;P;P

Vest4

0.62

MutPred

0.60

Gain of ubiquitination at E66 (P = 0.0031);Gain of ubiquitination at E66 (P = 0.0031);Gain of ubiquitination at E66 (P = 0.0031);Gain of ubiquitination at E66 (P = 0.0031);

MVP

0.55

MPC

0.13

ClinPred

0.90

GERP RS

5.3

Varity_R

0.23

gMVP

0.48

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over