Variant chr3-196371927-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015562.2(UBXN7):c.584A>G(p.Asn195Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,906 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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)

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: 5.02

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09240246).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBXN7	NM_015562.2 link	c.584A>G	p.Asn195Ser	missense_variant	6/11	ENST00000296328.9	NP_056377.1	O94888
UBXN7	XM_011512671.3 link	c.140A>G	p.Asn47Ser	missense_variant	5/10		XP_011510973.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
UBXN7	ENST00000296328.9 link	c.584A>G	p.Asn195Ser	missense_variant	6/11	1	NM_015562.2	ENSP00000296328.4	O94888
UBXN7	ENST00000428095.1 link	c.98A>G	p.Asn33Ser	missense_variant	2/7	1		ENSP00000397256.1	C9JAT7
UBXN7	ENST00000429160.1 link	n.*208A>G		non_coding_transcript_exon_variant	5/10	2		ENSP00000397238.1	F8WB69
UBXN7	ENST00000429160.1 link	n.*208A>G		3_prime_UTR_variant	5/10	2		ENSP00000397238.1	F8WB69

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460906

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726768

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 14, 2022

The c.584A>G (p.N195S) alteration is located in exon 6 (coding exon 6) of the UBXN7 gene. This alteration results from a A to G substitution at nucleotide position 584, causing the asparagine (N) at amino acid position 195 to be replaced by a serine (S). 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

0.072

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.028

T;T

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.080

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.96

D;D

M_CAP

Benign

0.0049

MetaRNN

Benign

0.092

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

N;.

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.47

N;N

REVEL

Benign

0.058

Sift

Benign

0.34

T;T

Sift4G

Benign

0.62

T;T

Polyphen

0.0050

B;.

Vest4

0.34

MutPred

0.27

Loss of methylation at K194 (P = 0.0909);.;

MVP

0.068

MPC

0.91

ClinPred

0.71

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.058

gMVP

0.47

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over