4-67701073-G-C

Variant names:

• chr4-67701073-G-C
• rs2109966366
• NM_018227.6:c.47C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018227.6(UBA6):​c.47C>G​(p.Ser16Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S16F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: UBA6 NM_018227.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.48
• Publications: 0 publications found

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-DT (HGNC:49083): (UBA6 divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBA6	NM_018227.6	c.47C>G	p.Ser16Cys	missense_variant	Exon 1 of 33	ENST00000322244.10	NP_060697.4
UBA6	XM_017008359.3	c.47C>G	p.Ser16Cys	missense_variant	Exon 1 of 33		XP_016863848.1
UBA6	XM_047415893.1	c.47C>G	p.Ser16Cys	missense_variant	Exon 1 of 28		XP_047271849.1
UBA6-DT	NR_015439.1	n.-205G>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBA6	ENST00000322244.10	c.47C>G	p.Ser16Cys	missense_variant	Exon 1 of 33	1	NM_018227.6	ENSP00000313454.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T;.
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.73	T;T
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.54	D;D
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	1.1	L;L
PhyloP100		3.5
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.094
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.054	T;T
Polyphen		1.0	D;D
Vest4		0.60
MutPred		0.23		Loss of disorder (P = 0.0202);Loss of disorder (P = 0.0202);
MVP		0.28
MPC		0.36
ClinPred		0.91	D
GERP RS		3.6
PromoterAI		-0.030	Neutral
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7
Varity_R		0.19
gMVP		0.49
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs2109966366; hg19: chr4-68566791;