rs141864081

Variant names:

• chr13-99238485-C-G
• rs141864081
• NM_001144072.2:c.90C>G

Your query was ambiguous. Multiple possible variants found:

• chr13-99238485-C-G
• chr13-99238485-C-T

Variant summary

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

The NM_177967.4(UBAC2):​c.215C>G​(p.Ser72Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S72L) has been classified as Likely benign.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: UBAC2 NM_177967.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.57
• 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]

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=0.12197113).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177967.4. 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.90C>G	p.Leu30Leu	synonymous	Exon 2 of 9	NP_001137544.1	Q8NBM4-1
	UBAC2	NM_177967.4		c.215C>G	p.Ser72Trp	missense	Exon 2 of 7	NP_808882.1	Q8NBM4-2
	UBAC2	NR_026644.2		n.773C>G		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.90C>G	p.Leu30Leu	synonymous	Exon 2 of 9	ENSP00000383911.3	Q8NBM4-1
	UBAC2	ENST00000376440.6	TSL:2	c.215C>G	p.Ser72Trp	missense	Exon 2 of 7	ENSP00000365623.2	Q8NBM4-2
	UBAC2	ENST00000961156.1		c.90C>G	p.Leu30Leu	synonymous	Exon 2 of 10	ENSP00000631215.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152156 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152156 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74330

African (AFR) AF: 0.00 AC: 0 AN: 41426

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.086	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	6.7
DANN	Uncertain	0.99
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
PhyloP100		2.6
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.072
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.077	T
Polyphen		0.0	B
Vest4		0.38
MutPred		0.27		Gain of catalytic residue at S72 (P = 0)
MVP		0.37
ClinPred		0.39	T
GERP RS		3.9
Mutation Taster		=89/11	polymorphism

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: rs141864081; hg19: chr13-99890739;