5-138084519-AGT-GGG

Variant names:

• chr5-138084519-AGT-GGG
• NM_001300939.2:c.178_180delAGTinsGGG
• WNT8A p.Ser60Gly

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001300939.2(WNT8A):​c.178_180delAGTinsGGG​(p.Ser60Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: WNT8A NM_001300939.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.60
• Publications: 0 publications found

Genes affected

WNT8A (HGNC:12788): (Wnt family member 8A) 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 is a member of the WNT gene family, and may be implicated in development of early embryos as well as germ cell tumors. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001300939.2. 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
	WNT8A	NM_001300939.2	MANE Select	c.178_180delAGTinsGGG	p.Ser60Gly	missense	N/A	NP_001287868.1	Q9H1J5-3
	WNT8A	NM_001300938.2		c.178_180delAGTinsGGG	p.Ser60Gly	missense	N/A	NP_001287867.1
	WNT8A	NM_058244.4		c.124_126delAGTinsGGG	p.Ser42Gly	missense	N/A	NP_490645.1	Q9H1J5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT8A	ENST00000506684.6	TSL:1 MANE Select	c.178_180delAGTinsGGG	p.Ser60Gly	missense	N/A	ENSP00000426653.1	Q9H1J5-3
	WNT8A	ENST00000504809.5	TSL:1	c.178_180delAGTinsGGG	p.Ser60Gly	missense	N/A	ENSP00000424809.1	D6RF94
	WNT8A	ENST00000398754.1	TSL:1	c.124_126delAGTinsGGG	p.Ser42Gly	missense	N/A	ENSP00000381739.1	Q9H1J5-1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.6

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-137420208;