6-99443598-AG-TA

Variant names:

• chr6-99443598-AG-TA
• NM_001346022.3:c.2039_2040delCTinsTA
• USP45 p.Ala680Val

Variant summary

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

The NM_001346022.3(USP45):​c.2039_2040delCTinsTA​(p.Ala680Val) variant causes a missense change. 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: USP45 NM_001346022.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.54
• Publications: 0 publications found

Genes affected

USP45 (HGNC:20080): (ubiquitin specific peptidase 45) The protein encoded by this gene is a deubiquitylase that binds ERCC1, the catalytic subunit of the XPF-ERCC1 DNA repair endonuclease. This endonuclease is a critical regulator of DNA repair processes, and the deubiquitylase activity of the encoded protein is important for maintaining the DNA repair ability of XPF-ERCC1. [provided by RefSeq, Sep 2016]

PNISR-AS1 (HGNC:40958): (PNISR antisense RNA 1)

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001346022.3. 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
	USP45	NM_001346022.3	MANE Select	c.2039_2040delCTinsTA	p.Ala680Val	missense	N/A	NP_001332951.1	Q70EL2-1
	USP45	NM_001080481.3		c.2039_2040delCTinsTA	p.Ala680Val	missense	N/A	NP_001073950.1	Q70EL2-1
	USP45	NM_001346021.3		c.2039_2040delCTinsTA	p.Ala680Val	missense	N/A	NP_001332950.1	Q70EL2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP45	ENST00000500704.7	TSL:5 MANE Select	c.2039_2040delCTinsTA	p.Ala680Val	missense	N/A	ENSP00000424372.1	Q70EL2-1
	USP45	ENST00000327681.10	TSL:1	c.2039_2040delCTinsTA	p.Ala680Val	missense	N/A	ENSP00000333376.6	Q70EL2-1
	USP45	ENST00000496518.6	TSL:1	n.*1005_*1006delCTinsTA		non_coding_transcript_exon	Exon 10 of 13	ENSP00000421248.1	H0Y8J5

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		4.5

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: chr6-99891474;