1-115651423-G-T

Variant names:

• chr1-115651423-G-T
• rs779768443
• NM_138959.3:c.10G>T

Variant summary

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

The NM_138959.3(VANGL1):​c.10G>T​(p.Glu4*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: VANGL1 NM_138959.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.26

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]

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 rank	MANE	Protein	UniProt
VANGL1	NM_138959.3	c.10G>T	p.Glu4*	stop_gained	Exon 2 of 8	ENST00000355485.7	NP_620409.1
VANGL1	NM_001172412.2	c.10G>T	p.Glu4*	stop_gained	Exon 2 of 8		NP_001165883.1
VANGL1	NM_001172411.2	c.10G>T	p.Glu4*	stop_gained	Exon 2 of 8		NP_001165882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VANGL1	ENST00000355485.7	c.10G>T	p.Glu4*	stop_gained	Exon 2 of 8	1	NM_138959.3	ENSP00000347672.2
VANGL1	ENST00000310260.7	c.10G>T	p.Glu4*	stop_gained	Exon 2 of 8	1		ENSP00000310800.3
VANGL1	ENST00000369509.1	c.10G>T	p.Glu4*	stop_gained	Exon 1 of 7	1		ENSP00000358522.1
VANGL1	ENST00000369510.8	c.10G>T	p.Glu4*	stop_gained	Exon 2 of 8	1		ENSP00000358523.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.60	D
BayesDel_noAF	Pathogenic	0.62
CADD	Pathogenic	43
DANN	Uncertain	1.0
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.95
FATHMM_MKL	Pathogenic	0.98	D
Vest4		0.83
GERP RS		4.9

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

Other links and lift over

dbSNP: rs779768443; hg19: chr1-116194044; COSMIC: COSV59622947;