chr1-115651423-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_138959.3(VANGL1):​c.10G>C​(p.Glu4Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E4K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: VANGL1 NM_138959.3 missense
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3090834).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VANGL1	NM_138959.3	c.10G>C	p.Glu4Gln	missense_variant	Exon 2 of 8	ENST00000355485.7	NP_620409.1
VANGL1	NM_001172412.2	c.10G>C	p.Glu4Gln	missense_variant	Exon 2 of 8		NP_001165883.1
VANGL1	NM_001172411.2	c.10G>C	p.Glu4Gln	missense_variant	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>C	p.Glu4Gln	missense_variant	Exon 2 of 8	1	NM_138959.3	ENSP00000347672.2
VANGL1	ENST00000310260.7	c.10G>C	p.Glu4Gln	missense_variant	Exon 2 of 8	1		ENSP00000310800.3
VANGL1	ENST00000369509.1	c.10G>C	p.Glu4Gln	missense_variant	Exon 1 of 7	1		ENSP00000358522.1
VANGL1	ENST00000369510.8	c.10G>C	p.Glu4Gln	missense_variant	Exon 2 of 8	1		ENSP00000358523.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461652 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727136

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 Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Uncertain	0.083	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T;.;T;T
Eigen	Uncertain	0.68
Eigen_PC	Pathogenic	0.66
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.97	D;D;.;.
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.31	T;T;T;T
MetaSVM	Uncertain	0.24	D
MutationAssessor	Benign	1.8	L;L;L;L
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-2.2	N;N;N;N
REVEL	Uncertain	0.35
Sift	Uncertain	0.0050	D;D;D;D
Sift4G	Uncertain	0.010	D;D;D;D
Polyphen		0.98	D;D;D;D
Vest4		0.44
MutPred		0.13		Gain of MoRF binding (P = 0.054);Gain of MoRF binding (P = 0.054);Gain of MoRF binding (P = 0.054);Gain of MoRF binding (P = 0.054);
MVP		0.58
MPC		0.49
ClinPred		0.91	D
GERP RS		4.9
Varity_R		0.28
gMVP		0.51

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.

Other links and lift over

hg19: chr1-116194044;