chr13-99280668-G-A

Variant names:

• chr13-99280668-G-A
• rs7999348
• NM_001144072.2:c.390-33429G>A

Variant summary

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

The NM_001144072.2(UBAC2):​c.390-33429G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 152,094 control chromosomes in the GnomAD database, including 24,967 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 0.55 (24967 hom., cov: 32)
• Consequence: UBAC2 NM_001144072.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.408
• Publications: 15 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144072.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBAC2	NM_001144072.2	MANE Select	c.390-33429G>A		intron	N/A	NP_001137544.1
	UBAC2	NM_177967.4		c.285-33429G>A		intron	N/A	NP_808882.1
	UBAC2	NR_026644.2		n.1073-33429G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBAC2	ENST00000403766.8	TSL:2 MANE Select	c.390-33429G>A		intron	N/A	ENSP00000383911.3
	UBAC2	ENST00000376440.6	TSL:2	c.285-33429G>A		intron	N/A	ENSP00000365623.2
	UBAC2	ENST00000355700.9	TSL:3	c.159+42114G>A		intron	N/A	ENSP00000347928.5

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82881 AN: 151976 Hom.: 24964 Cov.: 32

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.845

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.549

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

GnomAD4 genome AF: 0.545 AC: 82901 AN: 152094 Hom.: 24967 Cov.: 32 AF XY: 0.538 AC XY: 40023 AN XY: 74356

African (AFR) AF: 0.289 AC: 11962 AN: 41460

American (AMR) AF: 0.531 AC: 8128 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.620 AC: 2150 AN: 3468

East Asian (EAS) AF: 0.500 AC: 2587 AN: 5170

South Asian (SAS) AF: 0.388 AC: 1870 AN: 4820

European-Finnish (FIN) AF: 0.626 AC: 6620 AN: 10574

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.698 AC: 47477 AN: 67988

Other (OTH) AF: 0.545 AC: 1150 AN: 2112

Alfa AF: 0.637 Hom.: 40247

Bravo AF: 0.534

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.9
DANN	Benign	0.80
PhyloP100		-0.41
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: rs7999348; hg19: chr13-99932922;