Variant chr3-196407300-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_015562.2(UBXN7):c.167C>G(p.Ala56Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

UBXN7
NM_015562.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.10

Variant links:

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]

UBXN7 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27842063).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBXN7	NM_015562.2 link	c.167C>G	p.Ala56Gly	missense_variant	2/11	ENST00000296328.9	NP_056377.1	O94888
UBXN7	XM_011512671.3 link	c.-223-4281C>G		intron_variant			XP_011510973.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBXN7	ENST00000296328.9 link	c.167C>G	p.Ala56Gly	missense_variant	2/11	1	NM_015562.2	ENSP00000296328.4		O94888

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000802

AC:

AN:

249470

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135350

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000827

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 02, 2024

The c.167C>G (p.A56G) alteration is located in exon 2 (coding exon 2) of the UBXN7 gene. This alteration results from a C to G substitution at nucleotide position 167, causing the alanine (A) at amino acid position 56 to be replaced by a glycine (G). 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

0.18

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.024

T;.

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.94

D;D

M_CAP

Benign

0.016

MetaRNN

Benign

0.28

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.6

L;.

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.41

N;N

REVEL

Benign

0.18

Sift

Benign

0.041

D;D

Sift4G

Benign

0.29

T;.

Polyphen

0.73

P;P

Vest4

0.52

MutPred

0.20

Loss of glycosylation at P59 (P = 0.052);.;

MVP

0.082

MPC

1.2

ClinPred

0.44

GERP RS

5.4

Varity_R

0.19

gMVP

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over