17-9645744-C-T

Variant names:

• chr17-9645744-C-T
• rs891333808
• NM_153210.5:c.112C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153210.5(USP43):​c.112C>T​(p.Arg38Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000244 in 1,229,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R38G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000024 (0 hom.)
• Consequence: USP43 NM_153210.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.167
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21428159).

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.112C>T	p.Arg38Cys	missense	Exon 1 of 15	NP_694942.3
	USP43	NM_001267576.2		c.112C>T	p.Arg38Cys	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.112C>T	p.Arg38Cys	missense	Exon 1 of 15	ENSP00000285199.6	Q70EL4-1
	USP43	ENST00000570475.5	TSL:1	c.112C>T	p.Arg38Cys	missense	Exon 1 of 15	ENSP00000458963.1	Q70EL4-4
	USP43	ENST00000936734.1		c.112C>T	p.Arg38Cys	missense	Exon 1 of 15	ENSP00000606793.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000244 AC: 3 AN: 1229630 Hom.: 0 Cov.: 30 AF XY: 0.00000498 AC XY: 3 AN XY: 602162

African (AFR) AF: 0.00 AC: 0 AN: 24234

American (AMR) AF: 0.00 AC: 0 AN: 14460

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18820

East Asian (EAS) AF: 0.0000734 AC: 2 AN: 27246

South Asian (SAS) AF: 0.00 AC: 0 AN: 55274

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30476

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3512

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1005522

Other (OTH) AF: 0.0000200 AC: 1 AN: 50086

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.73	T
M_CAP	Pathogenic	0.60	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.17
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.044
Sift	Uncertain	0.027	D
Sift4G	Uncertain	0.018	D
Polyphen		0.016	B
Vest4		0.20
MutPred		0.30		Loss of methylation at R38 (P = 0.0149)
MVP		0.67
MPC		0.68
ClinPred		0.45	T
GERP RS		2.5
PromoterAI		0.0067	Neutral
Varity_R		0.088
gMVP		0.30
Mutation Taster		=91/9	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: rs891333808; hg19: chr17-9549061;