NM_014709.4:c.10286A>G

Variant names:

• chr2-61188457-T-C
• rs1385334130
• NM_014709.4:c.10286A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_014709.4(USP34):​c.10286A>G​(p.Asn3429Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,614,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N3429I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: USP34 NM_014709.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.200
• Publications: 0 publications found

Genes affected

USP34 (HGNC:20066): (ubiquitin specific peptidase 34) Enables cysteine-type endopeptidase activity and thiol-dependent deubiquitinase. Involved in positive regulation of canonical Wnt signaling pathway and protein K48-linked deubiquitination. Predicted to be active in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

AHSA2P (HGNC:):

AHSA2P (HGNC:20437): (activator of HSP90 ATPase homolog 2, pseudogene) Predicted to enable ATPase activator activity. Predicted to be involved in positive regulation of ATPase activity and protein folding. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.018172354).
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014709.4. 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
	USP34	NM_014709.4	MANE Select	c.10286A>G	p.Asn3429Ser	missense	Exon 80 of 80	NP_055524.3
	AHSA2P	NR_152210.1		n.2647T>C		non_coding_transcript_exon	Exon 6 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP34	ENST00000398571.7	TSL:5 MANE Select	c.10286A>G	p.Asn3429Ser	missense	Exon 80 of 80	ENSP00000381577.2	Q70CQ2-1
	AHSA2P	ENST00000394457.7	TSL:1	n.3828T>C		non_coding_transcript_exon	Exon 6 of 6
	USP34	ENST00000411912.5	TSL:5	c.3314A>G	p.Asn1105Ser	missense	Exon 26 of 26	ENSP00000398960.1	H7C183

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152242 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461892 Hom.: 0 Cov.: 33 AF XY: 0.00000688 AC XY: 5 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1112012

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152242 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74368

African (AFR) AF: 0.0000241 AC: 1 AN: 41474

American (AMR) AF: 0.00 AC: 0 AN: 15288

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000712 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	0.056
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.028
DANN	Benign	0.51
DEOGEN2	Benign	0.021	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.018	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	-0.81	N
PhyloP100		-0.20
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.065
Sift	Benign	0.69	T
Sift4G	Benign	0.87	T
Polyphen		0.0	B
Vest4		0.074
MutPred		0.072		Gain of phosphorylation at N3429 (P = 0.0051)
MVP		0.093
ClinPred		0.026	T
GERP RS		-8.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.031
gMVP		0.098
Mutation Taster		=98/2	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: rs1385334130; hg19: chr2-61415592;