chr13-99200922-C-G

Variant names:

• chr13-99200922-C-G
• rs1439678169
• NM_001144072.2:c.14C>G

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.14C>G​(p.Thr5Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000459 in 1,306,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 0.0000043 (0 hom.)
• Consequence: UBAC2 NM_001144072.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.74
• 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=0.2515978).

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.14C>G	p.Thr5Ser	missense	Exon 1 of 9	NP_001137544.1	Q8NBM4-1
	UBAC2	NM_177967.4		c.-490C>G		5_prime_UTR	Exon 1 of 7	NP_808882.1	Q8NBM4-2
	UBAC2	NR_026644.2		n.69C>G		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.14C>G	p.Thr5Ser	missense	Exon 1 of 9	ENSP00000383911.3	Q8NBM4-1
	UBAC2	ENST00000961156.1		c.14C>G	p.Thr5Ser	missense	Exon 1 of 10	ENSP00000631215.1
	UBAC2	ENST00000858721.1		c.14C>G	p.Thr5Ser	missense	Exon 1 of 10	ENSP00000528780.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152230 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: 0.00000433 AC: 5 AN: 1154462 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 552688

African (AFR) AF: 0.00 AC: 0 AN: 24636

American (AMR) AF: 0.00 AC: 0 AN: 15928

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15110

East Asian (EAS) AF: 0.000134 AC: 4 AN: 29750

South Asian (SAS) AF: 0.00 AC: 0 AN: 28580

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4628

European-Non Finnish (NFE) AF: 0.00000105 AC: 1 AN: 951468

Other (OTH) AF: 0.00 AC: 0 AN: 46020

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152230 Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1 AN XY: 74380

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000241 AC: 1 AN: 41466

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: 5186

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	Benign	0.13
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.024	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.71	T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		3.7
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.079
Sift	Benign	0.72	T
Sift4G	Uncertain	0.025	D
Polyphen		0.99	D
Vest4		0.44
MutPred		0.18		Gain of glycosylation at T5 (P = 0.0352)
MVP		0.63
MPC		1.1
ClinPred		0.94	D
GERP RS		4.7
PromoterAI		-0.024	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.18
gMVP		0.31
Mutation Taster		=68/32	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: rs1439678169; hg19: chr13-99853176;