13-99310638-C-T

Variant names:

• chr13-99310638-C-T
• rs9554581
• NM_001144072.2:c.390-3459C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001144072.2(UBAC2):​c.390-3459C>T 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 152,052 control chromosomes in the GnomAD database, including 1,616 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 (1616 hom., cov: 33)
• Consequence: UBAC2 NM_001144072.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.549
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBAC2	NM_001144072.2	c.390-3459C>T		intron_variant	Intron 4 of 8	ENST00000403766.8	NP_001137544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBAC2	ENST00000403766.8	c.390-3459C>T		intron_variant	Intron 4 of 8	2	NM_001144072.2	ENSP00000383911.3

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20359 AN: 151934 Hom.: 1607 Cov.: 33

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.0374

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.0890

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.140

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.134 AC: 20384 AN: 152052 Hom.: 1616 Cov.: 33 AF XY: 0.137 AC XY: 10190 AN XY: 74320

African (AFR) AF: 0.121 AC: 5001 AN: 41474

American (AMR) AF: 0.208 AC: 3180 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0890 AC: 309 AN: 3470

East Asian (EAS) AF: 0.322 AC: 1666 AN: 5170

South Asian (SAS) AF: 0.169 AC: 811 AN: 4812

European-Finnish (FIN) AF: 0.133 AC: 1398 AN: 10550

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7667 AN: 67996

Other (OTH) AF: 0.143 AC: 300 AN: 2104

Alfa AF: 0.143 Hom.: 304

Bravo AF: 0.141

Asia WGS AF: 0.256 AC: 888 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	18
DANN	Benign	0.70
PhyloP100		0.55
Mutation Taster		=100/0	polymorphism (auto)

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: rs9554581; hg19: chr13-99962892;