rs9517701

Positions:

• chr13-99377286-A-G
• chr13-99377286-A-T

Variant summary

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

The NM_001144072.2(UBAC2):​c.928-7942A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,338 control chromosomes in the GnomAD database, including 1,611 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 0.13 (1610 hom., cov: 33)
  • Exomes 𝑓: 0.088 (1 hom.)
• Consequence: UBAC2 NM_001144072.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37

Genes affected

UBAC2 (HGNC:20486): (UBA domain containing 2) Involved in negative regulation of canonical Wnt signaling pathway and negative regulation of retrograde protein transport, ER to cytosol. Acts upstream of or within protein localization to endoplasmic reticulum. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBAC2	NM_001144072.2	c.928-7942A>G		intron_variant		ENST00000403766.8	NP_001137544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBAC2	ENST00000403766.8	c.928-7942A>G		intron_variant		2	NM_001144072.2	ENSP00000383911	P1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20377 AN: 152152 Hom.: 1601 Cov.: 33

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.0890

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.139

GnomAD4 exome AF: 0.0882 AC: 6 AN: 68 Hom.: 1 Cov.: 0 AF XY: 0.100 AC XY: 4 AN XY: 40

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.167

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0893

GnomAD4 genome AF: 0.134 AC: 20403 AN: 152270 Hom.: 1610 Cov.: 33 AF XY: 0.137 AC XY: 10235 AN XY: 74470

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.0890

Gnomad4 EAS AF: 0.326

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.142

Alfa AF: 0.140 Hom.: 316

Bravo AF: 0.141

Asia WGS AF: 0.255 AC: 884 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.9
DANN	Benign	0.68

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: rs9517701; hg19: chr13-100029540;