NM_001144072.2:c.134T>C

Variant names:

• chr13-99238529-T-C
• NM_001144072.2:c.134T>C

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.134T>C​(p.Leu45Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UBAC2 NM_001144072.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.13
• Publications: 0 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: 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=0.21466953).

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.134T>C	p.Leu45Pro	missense	Exon 2 of 9	NP_001137544.1	Q8NBM4-1
	UBAC2	NM_177967.4		c.259T>C	p.Phe87Leu	missense	Exon 2 of 7	NP_808882.1	Q8NBM4-2
	UBAC2	NR_026644.2		n.817T>C		non_coding_transcript_exon	Exon 2 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBAC2	ENST00000403766.8	TSL:2 MANE Select	c.134T>C	p.Leu45Pro	missense	Exon 2 of 9	ENSP00000383911.3	Q8NBM4-1
	UBAC2	ENST00000961156.1		c.134T>C	p.Leu45Pro	missense	Exon 2 of 10	ENSP00000631215.1
	UBAC2	ENST00000858721.1		c.134T>C	p.Leu45Pro	missense	Exon 2 of 10	ENSP00000528780.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

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	Uncertain	0.42
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	27
DANN	Pathogenic	1.0
Eigen	Uncertain	0.66
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.60	T
PhyloP100		7.1
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.066
Sift	Benign	0.14	T
Sift4G	Benign	0.76	T
Polyphen		0.032	B
Vest4		0.27
MutPred		0.23		Gain of catalytic residue at T92 (P = 0.0101)
MVP		0.75
ClinPred		0.99	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.70
Mutation Taster		=39/61	disease causing

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

hg19: chr13-99890783;