chr3-55470054-G-A

Position:

• chr3-55470054-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_003392.7(WNT5A):​c.*38C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00974 in 1,610,436 control chromosomes in the GnomAD database, including 97 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0073 (3 hom., cov: 33)
  • Exomes 𝑓: 0.010 (94 hom.)
• Consequence: WNT5A NM_003392.7 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.24

Genes affected

WNT5A (HGNC:12784): (Wnt family member 5A) The WNT gene family consists of structurally related genes which encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene encodes a member of the WNT family that signals through both the canonical and non-canonical WNT pathways. This protein is a ligand for the seven transmembrane receptor frizzled-5 and the tyrosine kinase orphan receptor 2. This protein plays an essential role in regulating developmental pathways during embryogenesis. This protein may also play a role in oncogenesis. Mutations in this gene are the cause of autosomal dominant Robinow syndrome. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2012]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 3-55470054-G-A is Benign according to our data. Variant chr3-55470054-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 346265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 1110 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNT5A	NM_003392.7	c.*38C>T		3_prime_UTR_variant	5/5	ENST00000264634.9	NP_003383.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNT5A	ENST00000264634.9	c.*38C>T		3_prime_UTR_variant	5/5	1	NM_003392.7	ENSP00000264634	P1
WNT5A	ENST00000474267.5	c.*38C>T		3_prime_UTR_variant	6/6	5		ENSP00000417310	P1
WNT5A	ENST00000497027.5	c.*38C>T		3_prime_UTR_variant	5/5	2		ENSP00000420104
WNT5A	ENST00000493406.1	n.88C>T		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes AF: 0.00729 AC: 1110 AN: 152206 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00217

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.00707

Gnomad ASJ AF: 0.0135

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0120

Gnomad OTH AF: 0.0105

GnomAD3 exomes AF: 0.00694 AC: 1729 AN: 249192 Hom.: 12 AF XY: 0.00679 AC XY: 918 AN XY: 135252

Gnomad AFR exome AF: 0.00240

Gnomad AMR exome AF: 0.00481

Gnomad ASJ exome AF: 0.0112

Gnomad EAS exome AF: 0.000110

Gnomad SAS exome AF: 0.000654

Gnomad FIN exome AF: 0.00250

Gnomad NFE exome AF: 0.0114

Gnomad OTH exome AF: 0.00760

GnomAD4 exome AF: 0.00999 AC: 14568 AN: 1458112 Hom.: 94 Cov.: 29 AF XY: 0.00979 AC XY: 7105 AN XY: 725650

Gnomad4 AFR exome AF: 0.00231

Gnomad4 AMR exome AF: 0.00514

Gnomad4 ASJ exome AF: 0.0125

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.000732

Gnomad4 FIN exome AF: 0.00336

Gnomad4 NFE exome AF: 0.0118

Gnomad4 OTH exome AF: 0.00861

GnomAD4 genome AF: 0.00729 AC: 1110 AN: 152324 Hom.: 3 Cov.: 33 AF XY: 0.00652 AC XY: 486 AN XY: 74488

Gnomad4 AFR AF: 0.00216

Gnomad4 AMR AF: 0.00706

Gnomad4 ASJ AF: 0.0135

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00132

Gnomad4 NFE AF: 0.0120

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.00963 Hom.: 2

Bravo AF: 0.00836

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 28, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	16
DANN	Benign	0.87

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: rs62620048; hg19: chr3-55504082;