3-196407309-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The NM_015562.2(UBXN7):c.158G>A(p.Gly53Glu) 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: UBXN7 NM_015562.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.19

Genes affected

UBXN7 (HGNC:29119): (UBX domain protein 7) Enables ubiquitin binding activity and ubiquitin protein ligase binding activity. Located in nuclear body. Part of VCP-NPL4-UFD1 AAA ATPase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, UBXN7

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBXN7	NM_015562.2	c.158G>A	p.Gly53Glu	missense_variant	2/11	ENST00000296328.9
UBXN7	XM_011512671.3	c.-223-4290G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBXN7	ENST00000296328.9	c.158G>A	p.Gly53Glu	missense_variant	2/11	1	NM_015562.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Jul 19, 2023

The c.158G>A (p.G53E) alteration is located in exon 2 (coding exon 2) of the UBXN7 gene. This alteration results from a G to A substitution at nucleotide position 158, causing the glycine (G) at amino acid position 53 to be replaced by a glutamic acid (E). 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	Pathogenic	0.81
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
Cadd	Uncertain	24
Dann	Uncertain	0.99
DEOGEN2	Benign	0.067	T;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.57	D;D
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	0.70	N;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-2.1	N;D
REVEL	Benign	0.26
Sift	Benign	0.17	T;T
Sift4G	Benign	0.20	T;.
Polyphen		0.80	P;D
Vest4		0.78
MutPred		0.52		Gain of solvent accessibility (P = 0.0411);.;
MVP		0.30
MPC		1.9
ClinPred		0.96	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.33
gMVP		0.87

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: chr3-196134180; COSMIC: COSV56355343;