chr2-85616400-T-G

Position:

• chr2-85616400-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006590.4(USP39):​c.205T>G​(p.Phe69Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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: not found (cov: 32)
• Consequence: USP39 NM_006590.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.974

Genes affected

USP39 (HGNC:20071): (ubiquitin specific peptidase 39) Predicted to enable thiol-dependent deubiquitinase and zinc ion binding activity. Involved in spliceosomal complex assembly. Located in nucleoplasm. Part of U4/U6 x U5 tri-snRNP complex. [provided by Alliance of Genome Resources, Apr 2022]

USP39 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04897061).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP39	NM_006590.4	c.205T>G	p.Phe69Val	missense_variant	1/13	ENST00000323701.11	NP_006581.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP39	ENST00000323701.11	c.205T>G	p.Phe69Val	missense_variant	1/13	1	NM_006590.4	ENSP00000312981.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 07, 2024

The c.205T>G (p.F69V) alteration is located in exon 1 (coding exon 1) of the USP39 gene. This alteration results from a T to G substitution at nucleotide position 205, causing the phenylalanine (F) at amino acid position 69 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.7
DANN	Benign	0.33
DEOGEN2	Benign	0.0060	T;T;T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.59	T;.;T;T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.049	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	.;N;N;N
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	0.15	N;N;N;N
REVEL	Benign	0.021
Sift	Benign	0.53	T;T;T;T
Sift4G	Benign	0.53	T;T;T;T
Polyphen		0.0	B;B;B;.
Vest4		0.045
MutPred		0.34		Gain of sheet (P = 4e-04);Gain of sheet (P = 4e-04);Gain of sheet (P = 4e-04);Gain of sheet (P = 4e-04);
MVP		0.26
MPC		0.29
ClinPred		0.039	T
GERP RS		0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.051
gMVP		0.42

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-85843523;