3-55468138-TA-T

Variant names:

• chr3-55468138-TA-T
• rs78756487
• NM_003392.7:c.*1953delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

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

• Frequency:
  • Genomes: 𝑓 0.081 (668 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: WNT5A NM_003392.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0260
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 3-55468138-TA-T is Benign according to our data. Variant chr3-55468138-TA-T is described in ClinVar as Benign. ClinVar VariationId is 1247729.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

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.*1953delT		3_prime_UTR	Exon 5 of 5	NP_003383.4
	WNT5A	NM_001256105.1		c.*1953delT		3_prime_UTR	Exon 5 of 5	NP_001243034.1	P41221-2
	WNT5A	NM_001377271.1		c.*1953delT		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.*1953delT		3_prime_UTR	Exon 5 of 5	ENSP00000264634.4	P41221-1
	WNT5A	ENST00000474267.5	TSL:5	c.*1953delT		3_prime_UTR	Exon 6 of 6	ENSP00000417310.1	P41221-1

Frequencies

GnomAD3 genomes AF: 0.0807 AC: 10808 AN: 133902 Hom.: 667 Cov.: 0

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0878

Gnomad ASJ AF: 0.0757

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.0259

Gnomad MID AF: 0.112

Gnomad NFE AF: 0.0274

Gnomad OTH AF: 0.0865

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0808 AC: 10818 AN: 133908 Hom.: 668 Cov.: 0 AF XY: 0.0840 AC XY: 5347 AN XY: 63668

African (AFR) AF: 0.163 AC: 5994 AN: 36790

American (AMR) AF: 0.0879 AC: 1157 AN: 13166

Ashkenazi Jewish (ASJ) AF: 0.0757 AC: 249 AN: 3290

East Asian (EAS) AF: 0.103 AC: 472 AN: 4598

South Asian (SAS) AF: 0.215 AC: 880 AN: 4084

European-Finnish (FIN) AF: 0.0259 AC: 154 AN: 5938

Middle Eastern (MID) AF: 0.107 AC: 27 AN: 252

European-Non Finnish (NFE) AF: 0.0274 AC: 1727 AN: 63098

Other (OTH) AF: 0.0866 AC: 158 AN: 1824

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.026
Mutation Taster		=100/0	polymorphism (auto)

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;