Variant 1-62442213-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_003368.5(USP1):c.310G>A(p.Gly104Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000554 in 1,444,208 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

USP1
NM_003368.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.51

Variant links:

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]

USP1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP1	NM_003368.5 linkuse as main transcript	c.310G>A	p.Gly104Ser	missense_variant	4/9	ENST00000339950.5	NP_003359.3	O94782
USP1	NM_001017415.2 linkuse as main transcript	c.310G>A	p.Gly104Ser	missense_variant	4/9		NP_001017415.1	O94782
USP1	NM_001017416.2 linkuse as main transcript	c.310G>A	p.Gly104Ser	missense_variant	4/9		NP_001017416.1	O94782

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
USP1	ENST00000339950.5 linkuse as main transcript	c.310G>A	p.Gly104Ser	missense_variant	4/9	1	NM_003368.5	ENSP00000343526.4	O94782
USP1	ENST00000371146.5 linkuse as main transcript	c.310G>A	p.Gly104Ser	missense_variant	4/9	5		ENSP00000360188.1	O94782
USP1	ENST00000452143.5 linkuse as main transcript	c.310G>A	p.Gly104Ser	missense_variant	4/5	3		ENSP00000403662.1	C9JC88

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000554

AC:

AN:

1444208

Hom.:

Cov.:

AF XY:

0.00000696

AC XY:

AN XY:

718884

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000727

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 12, 2024

The c.310G>A (p.G104S) alteration is located in exon 4 (coding exon 3) of the USP1 gene. This alteration results from a G to A substitution at nucleotide position 310, causing the glycine (G) at amino acid position 104 to be replaced by a serine (S). 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

0.28

BayesDel_addAF

Uncertain

0.066

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.012

T;T;T

Eigen

Uncertain

0.65

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.88

D;D;.

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.51

D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

.;M;M

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-2.1

N;N;N

REVEL

Benign

0.25

Sift

Benign

0.064

T;T;T

Sift4G

Benign

0.18

T;D;D

Polyphen

1.0

.;D;D

Vest4

0.61, 0.62

MutPred

0.50

Gain of MoRF binding (P = 0.1221);Gain of MoRF binding (P = 0.1221);Gain of MoRF binding (P = 0.1221);

MVP

0.49

MPC

0.50

ClinPred

0.97

GERP RS

5.9

Varity_R

0.19

gMVP

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.38

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.38

Position offset: 2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over