rs6491493

chr13-99248166-G-C

Variant summary

Our verdict is Benign. Variant got -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

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=-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/exons	MANE	UniProt
UBAC2	NM_001144072.2	c.389+3542G>C		intron_variant		ENST00000403766.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBAC2	ENST00000403766.8	c.389+3542G>C		intron_variant		2	NM_001144072.2	P1

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

Gnomad4 AFR AF: 0.352

Gnomad4 AMR AF: 0.544

Gnomad4 ASJ AF: 0.638

Gnomad4 EAS AF: 0.502

Gnomad4 SAS AF: 0.459

Gnomad4 FIN AF: 0.628

Gnomad4 NFE AF: 0.712

Gnomad4 OTH AF: 0.571

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

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: rs6491493; hg19: chr13-99900420;