rs17575643

Variant names:

• chr13-99332421-C-T
• rs17575643
• NM_001144072.2:c.562-7899C>T

Variant summary

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

The NM_001144072.2(UBAC2):​c.562-7899C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0968 in 152,236 control chromosomes in the GnomAD database, including 804 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 0.097 (804 hom., cov: 32)
• Consequence: UBAC2 NM_001144072.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0420
• Publications: 10 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBAC2	NM_001144072.2	c.562-7899C>T		intron_variant	Intron 6 of 8	ENST00000403766.8	NP_001137544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBAC2	ENST00000403766.8	c.562-7899C>T		intron_variant	Intron 6 of 8	2	NM_001144072.2	ENSP00000383911.3

Frequencies

GnomAD3 genomes AF: 0.0968 AC: 14726 AN: 152118 Hom.: 795 Cov.: 32

Gnomad AFR AF: 0.0646

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.0720

Gnomad EAS AF: 0.0586

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.0637

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.100

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

GnomAD4 genome AF: 0.0968 AC: 14744 AN: 152236 Hom.: 804 Cov.: 32 AF XY: 0.0982 AC XY: 7306 AN XY: 74418

African (AFR) AF: 0.0645 AC: 2679 AN: 41534

American (AMR) AF: 0.163 AC: 2490 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0720 AC: 250 AN: 3470

East Asian (EAS) AF: 0.0585 AC: 303 AN: 5180

South Asian (SAS) AF: 0.0995 AC: 480 AN: 4826

European-Finnish (FIN) AF: 0.115 AC: 1219 AN: 10604

Middle Eastern (MID) AF: 0.0616 AC: 18 AN: 292

European-Non Finnish (NFE) AF: 0.104 AC: 7056 AN: 68010

Other (OTH) AF: 0.102 AC: 215 AN: 2112

Alfa AF: 0.103 Hom.: 1322

Bravo AF: 0.0991

Asia WGS AF: 0.0900 AC: 312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.8
DANN	Benign	0.72
PhyloP100		0.042
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: rs17575643; hg19: chr13-99984675;