rs753423982

Variant names:

• chr2-61190607-C-A
• rs753423982
• NM_014709.4:c.9640G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-61190607-C-A
• chr2-61190607-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014709.4(USP34):​c.9640G>T​(p.Ala3214Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,672 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. A3214T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: USP34 NM_014709.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.50

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:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26915634).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP34	NM_014709.4	c.9640G>T	p.Ala3214Ser	missense_variant	Exon 77 of 80	ENST00000398571.7	NP_055524.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP34	ENST00000398571.7	c.9640G>T	p.Ala3214Ser	missense_variant	Exon 77 of 80	5	NM_014709.4	ENSP00000381577.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461672 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727116

African (AFR) AF: 0.0000598 AC: 2 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111926

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.043	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.038	T;T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.27	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.20	N;.
PhyloP100		4.5
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.98	N;N
REVEL	Benign	0.19
Sift	Benign	0.59	T;T
Sift4G	Benign	0.18	T;T
Polyphen		0.050	B;.
Vest4		0.31
MutPred		0.35		Loss of helix (P = 0.0093);.;
MVP		0.50
ClinPred		0.47	T
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.18
gMVP		0.18
Mutation Taster		=85/15	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

Publications

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Other links and lift over

dbSNP: rs753423982; hg19: chr2-61417742;