17-9645788-C-A

Variant names:

• chr17-9645788-C-A
• rs1911342855
• NM_153210.5:c.156C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_153210.5(USP43):​c.156C>A​(p.His52Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000161 in 1,240,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: USP43 NM_153210.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.196
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048327446).

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.156C>A	p.His52Gln	missense	Exon 1 of 15	NP_694942.3
	USP43	NM_001267576.2		c.156C>A	p.His52Gln	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.156C>A	p.His52Gln	missense	Exon 1 of 15	ENSP00000285199.6	Q70EL4-1
	USP43	ENST00000570475.5	TSL:1	c.156C>A	p.His52Gln	missense	Exon 1 of 15	ENSP00000458963.1	Q70EL4-4
	USP43	ENST00000936734.1		c.156C>A	p.His52Gln	missense	Exon 1 of 15	ENSP00000606793.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000161 AC: 2 AN: 1240590 Hom.: 0 Cov.: 30 AF XY: 0.00000330 AC XY: 2 AN XY: 605708

African (AFR) AF: 0.00 AC: 0 AN: 23944

American (AMR) AF: 0.00 AC: 0 AN: 10890

Ashkenazi Jewish (ASJ) AF: 0.0000555 AC: 1 AN: 18020

East Asian (EAS) AF: 0.00 AC: 0 AN: 27466

South Asian (SAS) AF: 0.00 AC: 0 AN: 55132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3740

European-Non Finnish (NFE) AF: 9.86e-7 AC: 1 AN: 1014158

Other (OTH) AF: 0.00 AC: 0 AN: 50848

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Benign	0.084
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.8
DANN	Benign	0.71
DEOGEN2	Benign	0.020	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.16	T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.90	L
PhyloP100		-0.20
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.56	N
REVEL	Benign	0.065
Sift	Benign	0.21	T
Sift4G	Benign	0.32	T
Polyphen		0.0030	B
Vest4		0.044
MutPred		0.21		Loss of catalytic residue at H52 (P = 0.0269)
MVP		0.21
MPC		0.50
ClinPred		0.070	T
GERP RS		2.6
PromoterAI		0.0046	Neutral
Varity_R		0.041
gMVP		0.15

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: rs1911342855; hg19: chr17-9549105;