3-196391923-G-A

Variant summary

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

The NM_015562.2(UBXN7):c.358C>T(p.Arg120Trp) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000015 in 1,337,014 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: UBXN7 NM_015562.2 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.17

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.358C>T	p.Arg120Trp	missense_variant, splice_region_variant	5/11	ENST00000296328.9
UBXN7	XM_011512671.3	c.-87C>T		splice_region_variant, 5_prime_UTR_variant	4/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBXN7	ENST00000296328.9	c.358C>T	p.Arg120Trp	missense_variant, splice_region_variant	5/11	1	NM_015562.2	P1
UBXN7	ENST00000428095.1	c.-18-19881C>T		intron_variant		1
UBXN7	ENST00000381887.7	c.292C>T	p.Arg98Trp	missense_variant, splice_region_variant	4/4	3
UBXN7	ENST00000429160.1	c.210C>T	p.Phe70=	splice_region_variant, synonymous_variant, NMD_transcript_variant	4/10	2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000150 AC: 2 AN: 1337014 Hom.: 0 Cov.: 28 AF XY: 0.00000150 AC XY: 1 AN XY: 664864

Gnomad4 AFR exome AF: 0.0000337

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.70e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

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

Feb 16, 2023

The c.358C>T (p.R120W) alteration is located in exon 5 (coding exon 5) of the UBXN7 gene. This alteration results from a C to T substitution at nucleotide position 358, causing the arginine (R) at amino acid position 120 to be replaced by a tryptophan (W). 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	0.70
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
Cadd	Pathogenic	29
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.0	M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.21
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.026	D
Polyphen		1.0	D
Vest4		0.68
MutPred		0.43		Loss of disorder (P = 0.0011);
MVP		0.17
MPC		1.3
ClinPred		0.92	D
GERP RS		4.6
Varity_R		0.18
gMVP		0.76

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: chr3-196118794; COSMIC: COSV56354341; COSMIC: COSV56354341;