4-119239763-G-T

Variant names:

• chr4-119239763-G-T
• NM_001371395.1:c.4G>T

Variant summary

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

The NM_001371395.1(USP53):​c.4G>T​(p.Ala2Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,160 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: USP53 NM_001371395.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.60

Genes affected

USP53 (HGNC:29255): (ubiquitin specific peptidase 53) Predicted to enable thiol-dependent deubiquitinase. Predicted to be involved in response to auditory stimulus and sensory perception of sound. Predicted to act upstream of or within action potential and neuron apoptotic process. Predicted to be located in bicellular tight junction. Predicted to be active in cell-cell junction. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP53	NM_001371395.1	c.4G>T	p.Ala2Ser	missense_variant	Exon 5 of 19	ENST00000692078.1	NP_001358324.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP53	ENST00000692078.1	c.4G>T	p.Ala2Ser	missense_variant	Exon 5 of 19		NM_001371395.1	ENSP00000509606.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152042 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152160 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74390

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	0.0031	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	23
DANN	Benign	0.43
DEOGEN2	Benign	0.0095	T;T
Eigen	Benign	-0.076
Eigen_PC	Benign	-0.014
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.84	.;T
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.46	T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	0.70	N;N
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.20	N;N
REVEL	Benign	0.27
Sift	Benign	0.053	T;T
Sift4G	Benign	0.61	T;T
Polyphen		0.88	P;P
Vest4		0.45
MutPred		0.31		Gain of disorder (P = 0.018);Gain of disorder (P = 0.018);
MVP		0.71
MPC		0.54
ClinPred		0.75	D
GERP RS		4.3
Varity_R		0.082
gMVP		0.53

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: chr4-120160918;