rs375505955

Variant names:

• chr1-115659672-C-G
• rs375505955
• NM_138959.3:c.103C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-115659672-C-G
• chr1-115659672-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138959.3(VANGL1):​c.103C>G​(p.Arg35Gly) 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. 12/21 in silico tools predict 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. R35W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: VANGL1 NM_138959.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14870104).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VANGL1	NM_138959.3	c.103C>G	p.Arg35Gly	missense_variant	Exon 3 of 8	ENST00000355485.7	NP_620409.1
VANGL1	NM_001172412.2	c.103C>G	p.Arg35Gly	missense_variant	Exon 3 of 8		NP_001165883.1
VANGL1	NM_001172411.2	c.103C>G	p.Arg35Gly	missense_variant	Exon 3 of 8		NP_001165882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VANGL1	ENST00000355485.7	c.103C>G	p.Arg35Gly	missense_variant	Exon 3 of 8	1	NM_138959.3	ENSP00000347672.2
VANGL1	ENST00000310260.7	c.103C>G	p.Arg35Gly	missense_variant	Exon 3 of 8	1		ENSP00000310800.3
VANGL1	ENST00000369509.1	c.103C>G	p.Arg35Gly	missense_variant	Exon 2 of 7	1		ENSP00000358522.1
VANGL1	ENST00000369510.8	c.103C>G	p.Arg35Gly	missense_variant	Exon 3 of 8	1		ENSP00000358523.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251436 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135890

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.035	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.094	T;.;T;T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.89	D;D;.;.
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.15	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;L;L;L
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.6	N;N;N;N
REVEL	Uncertain	0.40
Sift	Benign	0.19	T;T;T;T
Sift4G	Benign	0.21	T;T;T;T
Polyphen		0.56	P;P;P;P
Vest4		0.27
MutPred		0.34		Loss of solvent accessibility (P = 0.0044);Loss of solvent accessibility (P = 0.0044);Loss of solvent accessibility (P = 0.0044);Loss of solvent accessibility (P = 0.0044);
MVP		0.44
MPC		0.21
ClinPred		0.48	T
GERP RS		1.3
Varity_R		0.082
gMVP		0.49

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: rs375505955; hg19: chr1-116202293;