NM_018227.6:c.1037+337G>C

Variant names:

• chr4-67662802-C-G
• rs11131719
• NM_018227.6:c.1037+337G>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018227.6(UBA6):​c.1037+337G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 185,828 control chromosomes in the GnomAD database, including 13,684 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.38 (11197 hom., cov: 33)
  • Exomes 𝑓: 0.37 (2487 hom.)
• Consequence: UBA6 NM_018227.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.456

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBA6	NM_018227.6	c.1037+337G>C		intron_variant	Intron 12 of 32	ENST00000322244.10	NP_060697.4
UBA6	XM_017008359.3	c.1037+337G>C		intron_variant	Intron 12 of 32		XP_016863848.1
UBA6	XM_047415893.1	c.1037+337G>C		intron_variant	Intron 12 of 27		XP_047271849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBA6	ENST00000322244.10	c.1037+337G>C		intron_variant	Intron 12 of 32	1	NM_018227.6	ENSP00000313454.4
UBA6	ENST00000420827.2	c.1037+337G>C		intron_variant	Intron 12 of 12	1		ENSP00000399234.2
UBA6	ENST00000429659.7	n.2072G>C		non_coding_transcript_exon_variant	Exon 11 of 11	2

Frequencies

GnomAD3 genomes AF: 0.382 AC: 57964 AN: 151864 Hom.: 11185 Cov.: 33

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.378

GnomAD4 exome AF: 0.370 AC: 12533 AN: 33844 Hom.: 2487 Cov.: 0 AF XY: 0.366 AC XY: 6451 AN XY: 17616

Gnomad4 AFR exome AF: 0.366

Gnomad4 AMR exome AF: 0.331

Gnomad4 ASJ exome AF: 0.418

Gnomad4 EAS exome AF: 0.294

Gnomad4 SAS exome AF: 0.307

Gnomad4 FIN exome AF: 0.395

Gnomad4 NFE exome AF: 0.383

Gnomad4 OTH exome AF: 0.369

GnomAD4 genome AF: 0.382 AC: 58011 AN: 151984 Hom.: 11197 Cov.: 33 AF XY: 0.380 AC XY: 28224 AN XY: 74294

Gnomad4 AFR AF: 0.368

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.424

Gnomad4 EAS AF: 0.320

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.393

Gnomad4 NFE AF: 0.396

Gnomad4 OTH AF: 0.375

Alfa AF: 0.220 Hom.: 448

Bravo AF: 0.383

Asia WGS AF: 0.303 AC: 1055 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.078
DANN	Benign	0.47

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

LitVar

Other links and lift over

dbSNP: rs11131719; hg19: chr4-68528520;