3-55468138-T-TAAA

Position:

• chr3-55468138-T-TAAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_003392.7(WNT5A):​c.*1953_*1954insTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.035 (123 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: WNT5A NM_003392.7 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0260

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 -10 ACMG points.

• BP6: Variant 3-55468138-T-TAAA is Benign according to our data. Variant chr3-55468138-T-TAAA is described in ClinVar as [Likely_benign]. Clinvar id is 1325973.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0345 (4622/133898) while in subpopulation NFE AF= 0.0514 (3245/63076). AF 95% confidence interval is 0.05. There are 123 homozygotes in gnomad4. There are 2162 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 4622 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNT5A	NM_003392.7	c.*1953_*1954insTTT		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.*1953_*1954insTTT		3_prime_UTR_variant	5/5	1	NM_003392.7	ENSP00000264634	P1
WNT5A	ENST00000474267.5	c.*1953_*1954insTTT		3_prime_UTR_variant	6/6	5		ENSP00000417310	P1

Frequencies

GnomAD3 genomes AF: 0.0345 AC: 4621 AN: 133890 Hom.: 123 Cov.: 0

Gnomad AFR AF: 0.0116

Gnomad AMI AF: 0.0472

Gnomad AMR AF: 0.0223

Gnomad ASJ AF: 0.0228

Gnomad EAS AF: 0.000433

Gnomad SAS AF: 0.0275

Gnomad FIN AF: 0.0641

Gnomad MID AF: 0.00719

Gnomad NFE AF: 0.0514

Gnomad OTH AF: 0.0243

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0345 AC: 4622 AN: 133898 Hom.: 123 Cov.: 0 AF XY: 0.0340 AC XY: 2162 AN XY: 63658

Gnomad4 AFR AF: 0.0116

Gnomad4 AMR AF: 0.0223

Gnomad4 ASJ AF: 0.0228

Gnomad4 EAS AF: 0.000435

Gnomad4 SAS AF: 0.0277

Gnomad4 FIN AF: 0.0641

Gnomad4 NFE AF: 0.0514

Gnomad4 OTH AF: 0.0242

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs78756487; hg19: chr3-55502166;