4-67701073-G-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018227.6(UBA6):​c.47C>T​(p.Ser16Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000089 in 1,461,484 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: UBA6 NM_018227.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.48

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

Verdict is Uncertain_significance. Variant got 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>T	p.Ser16Phe	missense_variant	Exon 1 of 33	ENST00000322244.10	NP_060697.4
UBA6	XM_017008359.3	c.47C>T	p.Ser16Phe	missense_variant	Exon 1 of 33		XP_016863848.1
UBA6	XM_047415893.1	c.47C>T	p.Ser16Phe	missense_variant	Exon 1 of 28		XP_047271849.1
UBA6-DT	NR_015439.1	n.-205G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBA6	ENST00000322244.10	c.47C>T	p.Ser16Phe	missense_variant	Exon 1 of 33	1	NM_018227.6	ENSP00000313454.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000890 AC: 13 AN: 1461484 Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6 AN XY: 727066

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: 0.0000108

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.47C>T (p.S16F) alteration is located in exon 1 (coding exon 1) of the UBA6 gene. This alteration results from a C to T substitution at nucleotide position 47, causing the serine (S) at amino acid position 16 to be replaced by a phenylalanine (F). 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	0.11
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T;.
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.80	T;T
M_CAP	Uncertain	0.20	D
MetaRNN	Uncertain	0.56	D;D
MetaSVM	Benign	-0.37	T
MutationAssessor	Benign	1.1	L;L
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.0	N;N
REVEL	Benign	0.080
Sift	Uncertain	0.0050	D;D
Sift4G	Uncertain	0.058	T;T
Polyphen		0.99	D;D
Vest4		0.62
MutPred		0.24		Loss of disorder (P = 0.0073);Loss of disorder (P = 0.0073);
MVP		0.27
MPC		0.22
ClinPred		0.83	D
GERP RS		3.6
Varity_R		0.18
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr4-68566791;