3-196362315-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_015562.2(UBXN7):c.1207G>C(p.Val403Leu) 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. 15/20 in silico tools predict a benign 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: 0.973

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, UBXN7
• BP4: Computational evidence support a benign effect (MetaRNN=0.068128884).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBXN7	NM_015562.2	c.1207G>C	p.Val403Leu	missense_variant	9/11	ENST00000296328.9
UBXN7	XM_011512671.3	c.763G>C	p.Val255Leu	missense_variant	8/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBXN7	ENST00000296328.9	c.1207G>C	p.Val403Leu	missense_variant	9/11	1	NM_015562.2	P1
UBXN7	ENST00000428095.1	c.721G>C	p.Val241Leu	missense_variant	5/7	1
UBXN7	ENST00000429160.1	c.*831G>C		3_prime_UTR_variant, NMD_transcript_variant	8/10	2

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

Jan 31, 2022

The c.1207G>C (p.V403L) alteration is located in exon 9 (coding exon 9) of the UBXN7 gene. This alteration results from a G to C substitution at nucleotide position 1207, causing the valine (V) at amino acid position 403 to be replaced by a leucine (L). 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	0.066
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
Cadd	Benign	14
Dann	Benign	0.97
DEOGEN2	Benign	0.025	T;T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.068	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.21	N;N
REVEL	Benign	0.083
Sift	Benign	0.46	T;T
Sift4G	Benign	0.30	T;T
Polyphen		0.0	B;.
Vest4		0.054
MutPred		0.28		Gain of relative solvent accessibility (P = 0.0479);.;
MVP		0.068
MPC		0.059
ClinPred		0.034	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.034
gMVP		0.24

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: rs1213370369; hg19: chr3-196089186;