17-9645810-G-C

Variant names:

• chr17-9645810-G-C
• rs1039977841
• NM_153210.5:c.178G>C

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.178G>C​(p.Gly60Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000288 in 1,389,326 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. G60S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000024 (0 hom.)
• Consequence: USP43 NM_153210.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11
• 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]

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=0.17840353).

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.178G>C	p.Gly60Arg	missense	Exon 1 of 15	NP_694942.3
	USP43	NM_001267576.2		c.178G>C	p.Gly60Arg	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.178G>C	p.Gly60Arg	missense	Exon 1 of 15	ENSP00000285199.6	Q70EL4-1
	USP43	ENST00000570475.5	TSL:1	c.178G>C	p.Gly60Arg	missense	Exon 1 of 15	ENSP00000458963.1	Q70EL4-4
	USP43	ENST00000936734.1		c.178G>C	p.Gly60Arg	missense	Exon 1 of 15	ENSP00000606793.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151950 Hom.: 0 Cov.: 32

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: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000242 AC: 3 AN: 1237376 Hom.: 0 Cov.: 30 AF XY: 0.00000332 AC XY: 2 AN XY: 602328

African (AFR) AF: 0.00 AC: 0 AN: 23778

American (AMR) AF: 0.00 AC: 0 AN: 10030

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17338

East Asian (EAS) AF: 0.00 AC: 0 AN: 27410

South Asian (SAS) AF: 0.0000368 AC: 2 AN: 54284

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3742

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1010818

Other (OTH) AF: 0.0000198 AC: 1 AN: 50626

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151950 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74216

African (AFR) AF: 0.00 AC: 0 AN: 41402

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67936

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.097	N
LIST_S2	Benign	0.63	T
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		1.1
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.072
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.35	B
Vest4		0.19
MutPred		0.37		Gain of methylation at G60 (P = 0.0197)
MVP		0.70
MPC		1.5
ClinPred		0.72	D
GERP RS		2.9
PromoterAI		-0.014	Neutral
Varity_R		0.11
gMVP		0.35
Mutation Taster		=94/6	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: rs1039977841; hg19: chr17-9549127;