15-90932481-CC-TA

Variant names:

• chr15-90932481-CC-TA
• NM_001286451.2:c.59_60delGGinsTA
• HDDC3 p.Arg20Leu

Variant summary

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

The NM_001286451.2(HDDC3):​c.59_60delGGinsTA​(p.Arg20Leu) variant causes a missense change involving the alteration of a non-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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R20P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: HDDC3 NM_001286451.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.510
• Publications: 0 publications found

Genes affected

HDDC3 (HGNC:30522): (HD domain containing 3) Predicted to enable guanosine-3',5'-bis(diphosphate) 3'-diphosphatase activity. [provided by Alliance of Genome Resources, Apr 2022]

UNC45A (HGNC:30594): (unc-45 myosin chaperone A) This gene encodes a regulatory component of the progesterone receptor/heat shock protein 90 chaperoning complex, which functions in the assembly and folding of the progesterone receptor. The encoded protein is thought to be essential for normal cell proliferation, and for the accumulation of myosin during development of muscle cells. [provided by RefSeq, Sep 2018]

UNC45A Gene-Disease associations (from GenCC):

• osteootohepatoenteric syndrome

  Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286451.2. 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
	HDDC3	NM_001286451.2	MANE Select	c.59_60delGGinsTA	p.Arg20Leu	missense	N/A	NP_001273380.1	Q8N4P3-1
	HDDC3	NM_198527.4		c.59_60delGGinsTA	p.Arg20Leu	missense	N/A	NP_940929.1	Q8N4P3-2
	UNC45A	NM_001039675.2		c.-759-1496_-759-1495delCCinsTA		intron	N/A	NP_001034764.1	Q9H3U1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDDC3	ENST00000394272.8	TSL:2 MANE Select	c.59_60delGGinsTA	p.Arg20Leu	missense	N/A	ENSP00000377814.4	Q8N4P3-1
	HDDC3	ENST00000559898.5	TSL:1	c.59_60delGGinsTA	p.Arg20Leu	missense	N/A	ENSP00000454103.1	H0YNP9
	HDDC3	ENST00000330334.7	TSL:1	c.59_60delGGinsTA	p.Arg20Leu	missense	N/A	ENSP00000330721.3	Q8N4P3-2

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.51

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: chr15-91475711;