1-62445363-G-A

Position:

• chr1-62445363-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003368.5(USP1):​c.1183G>A​(p.Gly395Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: USP1 NM_003368.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.34

Genes affected

USP1 (HGNC:12607): (ubiquitin specific peptidase 1) This gene encodes a member of the ubiquitin-specific processing (UBP) family of proteases that is a deubiquitinating enzyme (DUB) with His and Cys domains. This protein is located in the cytoplasm and cleaves the ubiquitin moiety from ubiquitin-fused precursors and ubiquitinylated proteins. The protein specifically deubiquitinates a protein in the Fanconi anemia (FA) DNA repair pathway. Alternate transcriptional splice variants have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.118326545).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP1	NM_003368.5	c.1183G>A	p.Gly395Arg	missense_variant	6/9	ENST00000339950.5	NP_003359.3
USP1	NM_001017415.2	c.1183G>A	p.Gly395Arg	missense_variant	6/9		NP_001017415.1
USP1	NM_001017416.2	c.1183G>A	p.Gly395Arg	missense_variant	6/9		NP_001017416.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP1	ENST00000339950.5	c.1183G>A	p.Gly395Arg	missense_variant	6/9	1	NM_003368.5	ENSP00000343526.4
USP1	ENST00000371146.5	c.1183G>A	p.Gly395Arg	missense_variant	6/9	5		ENSP00000360188.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 13, 2022

The c.1183G>A (p.G395R) alteration is located in exon 6 (coding exon 5) of the USP1 gene. This alteration results from a G to A substitution at nucleotide position 1183, causing the glycine (G) at amino acid position 395 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	20
DANN	Benign	0.73
DEOGEN2	Benign	0.10	T;T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.37
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.65	T;.
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;L
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.51	N;N
REVEL	Benign	0.092
Sift	Benign	0.18	T;T
Sift4G	Benign	0.41	T;T
Polyphen		0.0010	B;B
Vest4		0.13
MutPred		0.45		Gain of catalytic residue at G395 (P = 0.0598);Gain of catalytic residue at G395 (P = 0.0598);
MVP		0.23
MPC		0.12
ClinPred		0.30	T
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.079
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-62911034;