10-28533659-G-GGGCGGCGGCGGCGGGGGGC

Variant names:

• chr10-28533659-G-GGGCGGCGGCGGCGGGGGGC
• rs749860033
• NM_016628.5:c.41+50_41+51insCGGGGGGCGGCGGCGGCGG

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016628.5(WAC):​c.41+50_41+51insCGGGGGGCGGCGGCGGCGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: WAC NM_016628.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40

Genes affected

WAC (HGNC:17327): (WW domain containing adaptor with coiled-coil) The protein encoded by this gene contains a WW domain, which is a protein module found in a wide range of signaling proteins. This domain mediates protein-protein interactions and binds proteins containing short linear peptide motifs that are proline-rich or contain at least one proline. This gene product shares 94% sequence identity with the WAC protein in mouse, however, its exact function is not known. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WAC	NM_016628.5	c.41+50_41+51insCGGGGGGCGGCGGCGGCGG		intron_variant	Intron 1 of 13	ENST00000354911.9	NP_057712.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WAC	ENST00000354911.9	c.41+39_41+40insGGCGGCGGCGGCGGGGGGC		intron_variant	Intron 1 of 13	1	NM_016628.5	ENSP00000346986.4
WAC	ENST00000428935.6	c.-94-339_-94-338insGGCGGCGGCGGCGGGGGGC		intron_variant	Intron 1 of 7	2		ENSP00000399706.3
WAC	ENST00000651885.1	c.41+39_41+40insGGCGGCGGCGGCGGGGGGC		intron_variant	Intron 1 of 4			ENSP00000498678.1
WAC	ENST00000651598.1	c.-112-339_-112-338insGGCGGCGGCGGCGGGGGGC		intron_variant	Intron 1 of 5			ENSP00000498480.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

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: rs749860033; hg19: chr10-28822588;