chr17-9645720-C-T

Variant names:

• chr17-9645720-C-T
• rs1434204489
• NM_153210.5:c.88C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_153210.5(USP43):​c.88C>T​(p.Arg30Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000663 in 1,206,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R30G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000066 (0 hom.)
• Consequence: USP43 NM_153210.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.912
• Publications: 0 publications found

Genes affected

USP43 (HGNC:20072): (ubiquitin specific peptidase 43) Predicted to enable ISG15-specific protease activity. Predicted to be involved in translesion synthesis. Predicted to be located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CFAP52 (HGNC:16053): (cilia and flagella associated protein 52) WD repeat-containing proteins, such as WDR16, play crucial roles in a wide range of physiologic functions, including signal transduction, RNA processing, remodeling the cytoskeleton, regulation of vesicular traffic, and cell division (Silva et al., 2005 [PubMed 15967112]).[supplied by OMIM, Mar 2008]

CFAP52 Gene-Disease associations (from GenCC):

• situs inversus

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• visceral heterotaxy

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41628936).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153210.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP43	NM_153210.5	MANE Select	c.88C>T	p.Arg30Cys	missense	Exon 1 of 15	NP_694942.3
	USP43	NM_001267576.2		c.88C>T	p.Arg30Cys	missense	Exon 1 of 15	NP_001254505.1	Q70EL4-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP43	ENST00000285199.12	TSL:1 MANE Select	c.88C>T	p.Arg30Cys	missense	Exon 1 of 15	ENSP00000285199.6	Q70EL4-1
	USP43	ENST00000570475.5	TSL:1	c.88C>T	p.Arg30Cys	missense	Exon 1 of 15	ENSP00000458963.1	Q70EL4-4
	USP43	ENST00000936734.1		c.88C>T	p.Arg30Cys	missense	Exon 1 of 15	ENSP00000606793.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000663 AC: 8 AN: 1206888 Hom.: 0 Cov.: 30 AF XY: 0.00000339 AC XY: 2 AN XY: 589398

African (AFR) AF: 0.00 AC: 0 AN: 23950

American (AMR) AF: 0.00 AC: 0 AN: 13324

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17620

East Asian (EAS) AF: 0.00 AC: 0 AN: 26910

South Asian (SAS) AF: 0.00 AC: 0 AN: 50566

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3352

European-Non Finnish (NFE) AF: 0.00000805 AC: 8 AN: 993656

Other (OTH) AF: 0.00 AC: 0 AN: 48976

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.20
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.70	T
M_CAP	Pathogenic	0.75	D
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.91
PrimateAI	Pathogenic	0.95	D
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.27
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.24
MutPred		0.47		Loss of methylation at R30 (P = 0.0262)
MVP		0.60
MPC		0.68
ClinPred		0.99	D
GERP RS		3.4
PromoterAI		0.016	Neutral
Varity_R		0.38
gMVP		0.64
Mutation Taster		=80/20	polymorphism

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

Other links and lift over

dbSNP: rs1434204489; hg19: chr17-9549037;