rs7999348

Positions:

• chr13-99280668-G-A
• chr13-99280668-G-C
• chr13-99280668-G-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBAC2	NM_001144072.2	c.390-33429G>A		intron_variant		ENST00000403766.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBAC2	ENST00000403766.8	c.390-33429G>A		intron_variant		2	NM_001144072.2	P1

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

Gnomad4 AFR AF: 0.289

Gnomad4 AMR AF: 0.531

Gnomad4 ASJ AF: 0.620

Gnomad4 EAS AF: 0.500

Gnomad4 SAS AF: 0.388

Gnomad4 FIN AF: 0.626

Gnomad4 NFE AF: 0.698

Gnomad4 OTH AF: 0.545

Alfa AF: 0.654 Hom.: 31840

Bravo AF: 0.534

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.9
DANN	Benign	0.80

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: rs7999348; hg19: chr13-99932922;