1-115651481-A-C

Variant names:

• chr1-115651481-A-C
• NM_138959.3:c.68A>C

Variant summary

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

The NM_138959.3(VANGL1):​c.68A>C​(p.Gln23Pro) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: VANGL1 NM_138959.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.17

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=0.30290353).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VANGL1	NM_138959.3	c.68A>C	p.Gln23Pro	missense_variant	Exon 2 of 8	ENST00000355485.7	NP_620409.1
VANGL1	NM_001172412.2	c.68A>C	p.Gln23Pro	missense_variant	Exon 2 of 8		NP_001165883.1
VANGL1	NM_001172411.2	c.68A>C	p.Gln23Pro	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.68A>C	p.Gln23Pro	missense_variant	Exon 2 of 8	1	NM_138959.3	ENSP00000347672.2
VANGL1	ENST00000310260.7	c.68A>C	p.Gln23Pro	missense_variant	Exon 2 of 8	1		ENSP00000310800.3
VANGL1	ENST00000369509.1	c.68A>C	p.Gln23Pro	missense_variant	Exon 1 of 7	1		ENSP00000358522.1
VANGL1	ENST00000369510.8	c.68A>C	p.Gln23Pro	missense_variant	Exon 2 of 8	1		ENSP00000358523.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Sep 14, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.68A>C (p.Q23P) alteration is located in exon 2 (coding exon 1) of the VANGL1 gene. This alteration results from a A to C substitution at nucleotide position 68, causing the glutamine (Q) at amino acid position 23 to be replaced by a proline (P). 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	0.051
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;.;T;T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.74	T;T;.;.
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.30	T;T;T;T
MetaSVM	Benign	-0.47	T
MutationAssessor	Benign	1.6	L;L;L;L
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.7	N;N;N;N
REVEL	Uncertain	0.56
Sift	Benign	0.16	T;T;T;T
Sift4G	Benign	0.27	T;T;T;T
Polyphen		0.99	D;D;D;D
Vest4		0.41
MutPred		0.44		Gain of glycosylation at Q23 (P = 0.0714);Gain of glycosylation at Q23 (P = 0.0714);Gain of glycosylation at Q23 (P = 0.0714);Gain of glycosylation at Q23 (P = 0.0714);
MVP		0.31
MPC		0.46
ClinPred		0.78	D
GERP RS		3.7
Varity_R		0.18
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr1-116194102;