3-55468138-TAAAAAAA-TAAAA

Variant names:

• chr3-55468138-TAAA-T
• rs78756487
• NM_003392.7:c.*1951_*1953delTTT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_003392.7(WNT5A):​c.*1951_*1953delTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00041 (0 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: WNT5A NM_003392.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.561
• Publications: 0 publications found

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]

WNT5A Gene-Disease associations (from GenCC):

• autosomal dominant Robinow syndrome 1

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Illumina, Ambry Genetics
• autosomal dominant Robinow syndrome

  Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 55 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003392.7. 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
	WNT5A	NM_003392.7	MANE Select	c.*1951_*1953delTTT		3_prime_UTR	Exon 5 of 5	NP_003383.4
	WNT5A	NM_001256105.1		c.*1951_*1953delTTT		3_prime_UTR	Exon 5 of 5	NP_001243034.1	P41221-2
	WNT5A	NM_001377271.1		c.*1951_*1953delTTT		3_prime_UTR	Exon 5 of 5	NP_001364200.1	P41221-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT5A	ENST00000264634.9	TSL:1 MANE Select	c.*1951_*1953delTTT		3_prime_UTR	Exon 5 of 5	ENSP00000264634.4	P41221-1
	WNT5A	ENST00000474267.5	TSL:5	c.*1951_*1953delTTT		3_prime_UTR	Exon 6 of 6	ENSP00000417310.1	P41221-1

Frequencies

GnomAD3 genomes AF: 0.000403 AC: 54 AN: 133980 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000598

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000380

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000217

Gnomad SAS AF: 0.000243

Gnomad FIN AF: 0.000505

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000333

Gnomad OTH AF: 0.000551

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.000410 AC: 55 AN: 133988 Hom.: 0 Cov.: 0 AF XY: 0.000534 AC XY: 34 AN XY: 63698

African (AFR) AF: 0.000625 AC: 23 AN: 36828

American (AMR) AF: 0.000380 AC: 5 AN: 13174

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3290

East Asian (EAS) AF: 0.000217 AC: 1 AN: 4600

South Asian (SAS) AF: 0.000244 AC: 1 AN: 4092

European-Finnish (FIN) AF: 0.000505 AC: 3 AN: 5944

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 252

European-Non Finnish (NFE) AF: 0.000333 AC: 21 AN: 63118

Other (OTH) AF: 0.000549 AC: 1 AN: 1822

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.56
Mutation Taster		=100/0	polymorphism

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: rs78756487; hg19: chr3-55502166;