NM_138959.3:c.-171C>T

Variant names:

• chr1-115642053-C-T
• rs886045117
• NM_138959.3:c.-171C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138959.3(VANGL1):​c.-171C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,052 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.

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 30)
• Consequence: VANGL1 NM_138959.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• neural tube defects, susceptibility to

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138959.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VANGL1	NM_138959.3	MANE Select	c.-171C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	NP_620409.1	Q8TAA9-1
	VANGL1	NM_138959.3	MANE Select	c.-171C>T		5_prime_UTR	Exon 1 of 8	NP_620409.1	Q8TAA9-1
	VANGL1	NM_001172411.2		c.-171C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	NP_001165882.1	Q8TAA9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VANGL1	ENST00000355485.7	TSL:1 MANE Select	c.-171C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	ENSP00000347672.2	Q8TAA9-1
	VANGL1	ENST00000369510.8	TSL:1	c.-171C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	ENSP00000358523.3	Q8TAA9-2
	VANGL1	ENST00000355485.7	TSL:1 MANE Select	c.-171C>T		5_prime_UTR	Exon 1 of 8	ENSP00000347672.2	Q8TAA9-1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151052 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151052 Hom.: 0 Cov.: 30 AF XY: 0.0000136 AC XY: 1 AN XY: 73720

African (AFR) AF: 0.0000242 AC: 1 AN: 41238

American (AMR) AF: 0.00 AC: 0 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5050

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10288

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67712

Other (OTH) AF: 0.00 AC: 0 AN: 2074

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	19
DANN	Benign	0.95
PhyloP100		1.5
PromoterAI		-0.034	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs886045117; hg19: chr1-116184674;