rs891733535

Variant names:

• chr13-99200936-C-T
• rs891733535
• NM_001144072.2:c.28C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001144072.2(UBAC2):​c.28C>T​(p.Leu10Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000153 in 1,308,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 34)
  • Exomes 𝑓: 8.6e-7 (0 hom.)
• Consequence: UBAC2 NM_001144072.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.05
• Publications: 1 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]

UBAC2-AS1 (HGNC:42502): (UBAC2 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20488417).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBAC2	NM_001144072.2	MANE Select	c.28C>T	p.Leu10Phe	missense	Exon 1 of 9	NP_001137544.1	Q8NBM4-1
	UBAC2	NM_177967.4		c.-476C>T		5_prime_UTR	Exon 1 of 7	NP_808882.1	Q8NBM4-2
	UBAC2	NR_026644.2		n.83C>T		non_coding_transcript_exon	Exon 1 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBAC2	ENST00000403766.8	TSL:2 MANE Select	c.28C>T	p.Leu10Phe	missense	Exon 1 of 9	ENSP00000383911.3	Q8NBM4-1
	UBAC2	ENST00000961156.1		c.28C>T	p.Leu10Phe	missense	Exon 1 of 10	ENSP00000631215.1
	UBAC2	ENST00000858721.1		c.28C>T	p.Leu10Phe	missense	Exon 1 of 10	ENSP00000528780.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152242 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 8.65e-7 AC: 1 AN: 1156684 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 553542

African (AFR) AF: 0.00 AC: 0 AN: 24650

American (AMR) AF: 0.00 AC: 0 AN: 16358

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15124

East Asian (EAS) AF: 0.00 AC: 0 AN: 29836

South Asian (SAS) AF: 0.00 AC: 0 AN: 28612

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38558

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4636

European-Non Finnish (NFE) AF: 0.00000105 AC: 1 AN: 952758

Other (OTH) AF: 0.00 AC: 0 AN: 46152

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152242 Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1 AN XY: 74380

African (AFR) AF: 0.0000241 AC: 1 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.81	T
M_CAP	Pathogenic	0.29	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		1.0
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.088
Sift	Benign	0.047	D
Sift4G	Uncertain	0.017	D
Polyphen		0.0050	B
Vest4		0.30
MutPred		0.53		Loss of ubiquitination at K12 (P = 0.0787)
MVP		0.59
MPC		0.39
ClinPred		0.41	T
GERP RS		3.9
PromoterAI		-0.022	Neutral
Varity_R		0.17
gMVP		0.41
Mutation Taster		=58/42	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs891733535; hg19: chr13-99853190;