4-67630474-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_018227.6(UBA6):​c.2320G>A​(p.Ala774Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,433,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

UBA6
NM_018227.6 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.902
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.03170681).
BP6
Variant 4-67630474-C-T is Benign according to our data. Variant chr4-67630474-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3812749.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
UBA6NM_018227.6 linkc.2320G>A p.Ala774Thr missense_variant Exon 26 of 33 ENST00000322244.10 NP_060697.4 A0AVT1-1A1LT96
UBA6XM_017008359.3 linkc.2320G>A p.Ala774Thr missense_variant Exon 26 of 33 XP_016863848.1
UBA6XM_047415893.1 linkc.2320G>A p.Ala774Thr missense_variant Exon 26 of 28 XP_047271849.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
UBA6ENST00000322244.10 linkc.2320G>A p.Ala774Thr missense_variant Exon 26 of 33 1 NM_018227.6 ENSP00000313454.4 A0AVT1-1
UBA6ENST00000505673.2 linkc.790G>A p.Ala264Thr missense_variant Exon 9 of 9 5 ENSP00000421984.2 H0Y8S8

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000139
AC:
2
AN:
1433822
Hom.:
0
Cov.:
29
AF XY:
0.00000141
AC XY:
1
AN XY:
711362
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:
0.0000245
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Dec 21, 2024
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.057
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
14
DANN
Benign
0.29
DEOGEN2
Benign
0.081
T
Eigen
Benign
-0.97
Eigen_PC
Benign
-0.70
FATHMM_MKL
Benign
0.12
N
LIST_S2
Benign
0.068
T
M_CAP
Benign
0.0035
T
MetaRNN
Benign
0.032
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-1.8
N
PrimateAI
Benign
0.36
T
PROVEAN
Benign
1.1
N
REVEL
Benign
0.057
Sift
Benign
0.84
T
Sift4G
Benign
0.68
T
Polyphen
0.0
B
Vest4
0.099
MutPred
0.35
Gain of helix (P = 0.2684);
MVP
0.043
MPC
0.14
ClinPred
0.23
T
GERP RS
2.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.016
gMVP
0.10

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-68496192; API