rs4504482

Variant names:

• chr6-99446062-T-A
• rs4504482
• NM_001346022.3:c.1710A>T

Your query was ambiguous. Multiple possible variants found:

• chr6-99446062-T-A
• chr6-99446062-T-C
• chr6-99446062-T-G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001346022.3(USP45):​c.1710A>T​(p.Gly570Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G570G) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: USP45 NM_001346022.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.186
• Publications: 27 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=0.186 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP45	NM_001346022.3	MANE Select	c.1710A>T	p.Gly570Gly	synonymous	Exon 14 of 18	NP_001332951.1
	USP45	NM_001080481.3		c.1710A>T	p.Gly570Gly	synonymous	Exon 14 of 18	NP_001073950.1
	USP45	NM_001346021.3		c.1710A>T	p.Gly570Gly	synonymous	Exon 14 of 18	NP_001332950.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP45	ENST00000500704.7	TSL:5 MANE Select	c.1710A>T	p.Gly570Gly	synonymous	Exon 14 of 18	ENSP00000424372.1
	USP45	ENST00000327681.10	TSL:1	c.1710A>T	p.Gly570Gly	synonymous	Exon 14 of 18	ENSP00000333376.6
	USP45	ENST00000496518.6	TSL:1	n.*676A>T		non_coding_transcript_exon	Exon 9 of 13	ENSP00000421248.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 48

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 23591

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.3
DANN	Benign	0.52
PhyloP100		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4504482; hg19: chr6-99893938;