11-11884509-A-C

Position:

• chr11-11884509-A-C

Variant summary

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

The NM_001282659.2(USP47):​c.286A>C​(p.Asn96His) 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. 13/21 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: USP47 NM_001282659.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.88

Genes affected

USP47 (HGNC:20076): (ubiquitin specific peptidase 47) Enables WD40-repeat domain binding activity and thiol-dependent deubiquitinase. Involved in several processes, including monoubiquitinated protein deubiquitination; negative regulation of G2/M transition of mitotic cell cycle; and negative regulation of nitrogen compound metabolic process. Located in cytoplasm. Part of SCF ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

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=0.18660948).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP47	NM_001282659.2	c.286A>C	p.Asn96His	missense_variant	3/28	ENST00000527733.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP47	ENST00000527733.7	c.286A>C	p.Asn96His	missense_variant	3/28	1	NM_001282659.2	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Dec 20, 2023

The c.82A>C (p.N28H) alteration is located in exon 2 (coding exon 2) of the USP47 gene. This alteration results from a A to C substitution at nucleotide position 82, causing the asparagine (N) at amino acid position 28 to be replaced by a histidine (H). 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	0.074
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	20
DANN	Uncertain	0.99
Eigen	Benign	0.099
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.84	T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;N;N;N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.7	N;N;N
REVEL	Benign	0.076
Sift	Benign	0.11	T;D;D
Sift4G	Uncertain	0.022	D;D;D
Polyphen		0.59	P;.;.
Vest4		0.26
MutPred		0.29		Gain of helix (P = 0.0078);.;.;
MVP		0.40
MPC		0.48
ClinPred		0.76	D
GERP RS		4.5
Varity_R		0.079
gMVP		0.25

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: chr11-11906056;