3-196356776-C-T

Position:

• chr3-196356776-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_015562.2(UBXN7):​c.1379G>A​(p.Arg460Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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: 7.82

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.911

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBXN7	NM_015562.2	c.1379G>A	p.Arg460Gln	missense_variant	11/11	ENST00000296328.9	NP_056377.1
UBXN7	XM_011512671.3	c.935G>A	p.Arg312Gln	missense_variant	10/10		XP_011510973.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBXN7	ENST00000296328.9	c.1379G>A	p.Arg460Gln	missense_variant	11/11	1	NM_015562.2	ENSP00000296328.4
UBXN7	ENST00000428095.1	c.893G>A	p.Arg298Gln	missense_variant	7/7	1		ENSP00000397256.1
UBXN7	ENST00000429160.1	n.*1003G>A		non_coding_transcript_exon_variant	10/10	2		ENSP00000397238.1
UBXN7	ENST00000429160.1	n.*1003G>A		3_prime_UTR_variant	10/10	2		ENSP00000397238.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000468 Hom.: 0

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 09, 2024

The c.1379G>A (p.R460Q) alteration is located in exon 11 (coding exon 11) of the UBXN7 gene. This alteration results from a G to A substitution at nucleotide position 1379, causing the arginine (R) at amino acid position 460 to be replaced by a glutamine (Q). 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	0.96
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.38
CADD	Pathogenic	30
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.16	T;T
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Benign	0.029	D
MetaRNN	Pathogenic	0.91	D;D
MetaSVM	Uncertain	0.054	D
MutationAssessor	Pathogenic	3.0	M;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-2.2	N;N
REVEL	Uncertain	0.50
Sift	Uncertain	0.0070	D;D
Sift4G	Uncertain	0.013	D;D
Polyphen		1.0	D;.
Vest4		0.75
MutPred		0.87		Loss of glycosylation at P459 (P = 0.0472);.;
MVP		0.61
MPC		2.9
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.78
gMVP		0.85

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: rs1728360089; hg19: chr3-196083647;