rs372729949

Variant names:

• chr2-61188143-C-G
• rs372729949
• NM_014709.4:c.10600G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-61188143-C-G
• chr2-61188143-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014709.4(USP34):​c.10600G>C​(p.Val3534Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: USP34 NM_014709.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.89

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: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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1713483).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP34	NM_014709.4	c.10600G>C	p.Val3534Leu	missense_variant	Exon 80 of 80	ENST00000398571.7	NP_055524.3
AHSA2P	NR_152210.1	n.2333C>G		non_coding_transcript_exon_variant	Exon 6 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP34	ENST00000398571.7	c.10600G>C	p.Val3534Leu	missense_variant	Exon 80 of 80	5	NM_014709.4	ENSP00000381577.2
AHSA2P	ENST00000394457.7	n.3514C>G		non_coding_transcript_exon_variant	Exon 6 of 6	1
USP34	ENST00000411912.5	c.3628G>C	p.Val1210Leu	missense_variant	Exon 26 of 26	5		ENSP00000398960.1
USP34	ENST00000436269.1	c.1234G>C	p.Val412Leu	missense_variant	Exon 7 of 7	5		ENSP00000398489.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152108 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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152108 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74312

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.036	T;T
Eigen	Benign	-0.17
Eigen_PC	Benign	0.024
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.55	N;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.87	N;N
REVEL	Benign	0.088
Sift	Benign	0.066	T;T
Sift4G	Benign	0.072	T;D
Polyphen		0.0	B;.
Vest4		0.29
MutPred		0.36		Gain of catalytic residue at V3534 (P = 0.0028);.;
MVP		0.043
ClinPred		0.51	D
GERP RS		4.7
Varity_R		0.17
gMVP		0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs372729949; hg19: chr2-61415278;