chr4-67619092-C-A

Position:

• chr4-67619092-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018227.6(UBA6):​c.3064G>T​(p.Val1022Leu) 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)
• Consequence: UBA6 NM_018227.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.91

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]

ACMG classification

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=0.37853736).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBA6	NM_018227.6	c.3064G>T	p.Val1022Leu	missense_variant	33/33	ENST00000322244.10	NP_060697.4
UBA6	XM_017008359.3	c.3024-28G>T		intron_variant			XP_016863848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBA6	ENST00000322244.10	c.3064G>T	p.Val1022Leu	missense_variant	33/33	1	NM_018227.6	ENSP00000313454.4
UBA6	ENST00000514261.1	n.*119G>T		non_coding_transcript_exon_variant	4/4	5		ENSP00000425091.1
UBA6	ENST00000514261.1	n.*119G>T		3_prime_UTR_variant	4/4	5		ENSP00000425091.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

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

Mar 01, 2023

The c.3064G>T (p.V1022L) alteration is located in exon 33 (coding exon 33) of the UBA6 gene. This alteration results from a G to T substitution at nucleotide position 3064, causing the valine (V) at amino acid position 1022 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	Uncertain	0.47
BayesDel_addAF	Uncertain	0.031	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.94	L
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.16
Sift	Benign	0.31	T
Sift4G	Benign	0.26	T
Polyphen		0.91	P
Vest4		0.55
MutPred		0.46		Gain of glycosylation at Y1021 (P = 0.0047);
MVP		0.23
MPC		0.15
ClinPred		0.93	D
GERP RS		4.9
Varity_R		0.23
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: chr4-68484810;