17-9645733-C-T

Variant names:

• chr17-9645733-C-T
• rs944285870
• NM_153210.5:c.101C>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.101C>T​(p.Ala34Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000219 in 1,371,696 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. A34E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: USP43 NM_153210.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.51
• 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=0.16962838).

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.101C>T	p.Ala34Val	missense	Exon 1 of 15	NP_694942.3
	USP43	NM_001267576.2		c.101C>T	p.Ala34Val	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.101C>T	p.Ala34Val	missense	Exon 1 of 15	ENSP00000285199.6	Q70EL4-1
	USP43	ENST00000570475.5	TSL:1	c.101C>T	p.Ala34Val	missense	Exon 1 of 15	ENSP00000458963.1	Q70EL4-4
	USP43	ENST00000936734.1		c.101C>T	p.Ala34Val	missense	Exon 1 of 15	ENSP00000606793.1

Frequencies

GnomAD3 genomes AF: 0.00000660 AC: 1 AN: 151464 Hom.: 0 Cov.: 31

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: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000164 AC: 2 AN: 1220232 Hom.: 0 Cov.: 30 AF XY: 0.00000168 AC XY: 1 AN XY: 596806

African (AFR) AF: 0.00 AC: 0 AN: 24102

American (AMR) AF: 0.00 AC: 0 AN: 13998

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18280

East Asian (EAS) AF: 0.00 AC: 0 AN: 27138

South Asian (SAS) AF: 0.00 AC: 0 AN: 53292

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29498

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3450

European-Non Finnish (NFE) AF: 0.00000200 AC: 2 AN: 1000860

Other (OTH) AF: 0.00 AC: 0 AN: 49614

GnomAD4 genome AF: 0.00000660 AC: 1 AN: 151464 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 73958

African (AFR) AF: 0.00 AC: 0 AN: 41328

American (AMR) AF: 0.00 AC: 0 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5096

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10442

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67810

Other (OTH) AF: 0.00 AC: 0 AN: 2080

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.53	T
M_CAP	Pathogenic	0.32	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		2.5
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.050	N
REVEL	Benign	0.050
Sift	Benign	0.29	T
Sift4G	Benign	0.28	T
Polyphen		0.40	B
Vest4		0.15
MutPred		0.35		Gain of sheet (P = 0.0036)
MVP		0.40
MPC		0.49
ClinPred		0.26	T
GERP RS		2.1
PromoterAI		-0.060	Neutral
Varity_R		0.051
gMVP		0.28

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: rs944285870; hg19: chr17-9549050;