chr13-99238545-C-T

Variant names:

• chr13-99238545-C-T
• rs1271534240
• NM_001144072.2:c.150C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_177967.4(UBAC2):​c.275C>T​(p.Thr92Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,456,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: UBAC2 NM_177967.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.866
• 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.053666353).
• BP6: Variant 13-99238545-C-T is Benign according to our data. Variant chr13-99238545-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3812784.Status of the report is criteria_provided_single_submitter, 1 stars.

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.150C>T	p.Asn50Asn	synonymous	Exon 2 of 9	NP_001137544.1	Q8NBM4-1
	UBAC2	NM_177967.4		c.275C>T	p.Thr92Met	missense	Exon 2 of 7	NP_808882.1	Q8NBM4-2
	UBAC2	NR_026644.2		n.833C>T		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.150C>T	p.Asn50Asn	synonymous	Exon 2 of 9	ENSP00000383911.3	Q8NBM4-1
	UBAC2	ENST00000376440.6	TSL:2	c.275C>T	p.Thr92Met	missense	Exon 2 of 7	ENSP00000365623.2	Q8NBM4-2
	UBAC2	ENST00000961156.1		c.150C>T	p.Asn50Asn	synonymous	Exon 2 of 10	ENSP00000631215.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 250226 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1456220 Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 2 AN XY: 724560

African (AFR) AF: 0.00 AC: 0 AN: 33446

American (AMR) AF: 0.00 AC: 0 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25986

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85542

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52320

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1108748

Other (OTH) AF: 0.00 AC: 0 AN: 60090

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.14
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	1.4
DANN	Benign	0.95
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.87
PROVEAN	Benign	-0.24	N
REVEL	Benign	0.018
Sift	Benign	0.056	T
Sift4G	Benign	0.27	T
Polyphen		0.24	B
Vest4		0.22
MutPred		0.33		Gain of catalytic residue at A97 (P = 0.0174)
MVP		0.13
ClinPred		0.061	T
GERP RS		-6.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=95/5	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: rs1271534240; hg19: chr13-99890799;