NM_153210.5:c.541A>G

Variant names:

• chr17-9656439-A-G
• rs1442246415
• NM_153210.5:c.541A>G

Variant summary

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

The NM_153210.5(USP43):​c.541A>G​(p.Asn181Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: USP43 NM_153210.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.33
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.541A>G	p.Asn181Asp	missense	Exon 2 of 15	NP_694942.3
	USP43	NM_001267576.2		c.541A>G	p.Asn181Asp	missense	Exon 2 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.541A>G	p.Asn181Asp	missense	Exon 2 of 15	ENSP00000285199.6	Q70EL4-1
	USP43	ENST00000570475.5	TSL:1	c.541A>G	p.Asn181Asp	missense	Exon 2 of 15	ENSP00000458963.1	Q70EL4-4
	USP43	ENST00000574408.5	TSL:1	c.3A>G	p.Ala1Ala	synonymous	Exon 1 of 13	ENSP00000459328.3	V9GXZ5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.54
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.6	L
PhyloP100		6.3
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.22
Sift	Uncertain	0.025	D
Sift4G	Uncertain	0.049	D
Polyphen		1.0	D
Vest4		0.59
MutPred		0.63		Loss of loop (P = 0.0986)
MVP		0.79
MPC		1.4
ClinPred		0.98	D
GERP RS		4.0
PromoterAI		0.0048	Neutral
Varity_R		0.63
gMVP		0.51

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: rs1442246415; hg19: chr17-9559756;