rs6491493

Variant names:

• chr13-99248166-G-C
• rs6491493
• NM_001144072.2:c.389+3542G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001144072.2(UBAC2):​c.389+3542G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 151,844 control chromosomes in the GnomAD database, including 26,789 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 0.57 (26789 hom., cov: 30)
• Consequence: UBAC2 NM_001144072.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.267
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBAC2	NM_001144072.2	c.389+3542G>C		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.389+3542G>C		intron_variant	Intron 4 of 8	2	NM_001144072.2	ENSP00000383911.3

Frequencies

GnomAD3 genomes AF: 0.574 AC: 87021 AN: 151726 Hom.: 26778 Cov.: 30

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.876

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.643

Gnomad NFE AF: 0.712

Gnomad OTH AF: 0.572

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

GnomAD4 genome AF: 0.573 AC: 87071 AN: 151844 Hom.: 26789 Cov.: 30 AF XY: 0.567 AC XY: 42045 AN XY: 74194

African (AFR) AF: 0.352 AC: 14573 AN: 41344

American (AMR) AF: 0.544 AC: 8309 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 2214 AN: 3470

East Asian (EAS) AF: 0.502 AC: 2602 AN: 5180

South Asian (SAS) AF: 0.459 AC: 2207 AN: 4810

European-Finnish (FIN) AF: 0.628 AC: 6600 AN: 10506

Middle Eastern (MID) AF: 0.661 AC: 193 AN: 292

European-Non Finnish (NFE) AF: 0.712 AC: 48372 AN: 67950

Other (OTH) AF: 0.571 AC: 1204 AN: 2110

Alfa AF: 0.549 Hom.: 1915

Bravo AF: 0.561

Asia WGS AF: 0.421 AC: 1468 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	1.2
DANN	Benign	0.39
PhyloP100		-0.27
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: rs6491493; hg19: chr13-99900420;