Variant 4-67631711-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_018227.6(UBA6):c.2255C>A(p.Pro752His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

UBA6
NM_018227.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.08

Variant links:

Genes affected

UBA6 (HGNC:25581): (ubiquitin like modifier activating enzyme 6) Modification of proteins with ubiquitin (UBB; MIM 191339) or ubiquitin-like proteins controls many signaling networks and requires a ubiquitin-activating enzyme (E1), a ubiquitin conjugating enzyme (E2), and a ubiquitin protein ligase (E3). UBE1L2 is an E1 enzyme that initiates the activation and conjugation of ubiquitin-like proteins (Jin et al., 2007 [PubMed 17597759]).[supplied by OMIM, Mar 2008]

UBA6 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=0.35506165).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBA6	NM_018227.6 link	c.2255C>A	p.Pro752His	missense_variant	25/33	ENST00000322244.10	NP_060697.4	A0AVT1-1A1LT96
UBA6	XM_017008359.3 link	c.2255C>A	p.Pro752His	missense_variant	25/33		XP_016863848.1
UBA6	XM_047415893.1 link	c.2255C>A	p.Pro752His	missense_variant	25/28		XP_047271849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBA6	ENST00000322244.10 link	c.2255C>A	p.Pro752His	missense_variant	25/33	1	NM_018227.6	ENSP00000313454.4		A0AVT1-1
UBA6	ENST00000505673.2 link	c.725C>A	p.Pro242His	missense_variant	8/9	5		ENSP00000421984.2		H0Y8S8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1451962

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722446

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:

0.00

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

Apr 20, 2023

The c.2255C>A (p.P752H) alteration is located in exon 25 (coding exon 25) of the UBA6 gene. This alteration results from a C to A substitution at nucleotide position 2255, causing the proline (P) at amino acid position 752 to be replaced by a histidine (H). 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

0.12

BayesDel_addAF

Benign

-0.022

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.53

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.80

M_CAP

Benign

0.050

MetaRNN

Benign

0.36

MetaSVM

Benign

-0.63

MutationAssessor

Pathogenic

3.2

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.21

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.013

Polyphen

0.90

Vest4

0.45

MutPred

0.39

Gain of helix (P = 0.062);

MVP

0.13

MPC

0.47

ClinPred

0.99

GERP RS

5.0

Varity_R

0.33

gMVP

0.28

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