NM_001370062.2:c.2761A>T

Variant names:

• chr9-33923830-T-A
• rs771487841
• NM_001370062.2:c.2761A>T

Variant summary

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

The NM_001370062.2(UBAP2):​c.2761A>T​(p.Met921Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000041 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000041 (0 hom.)
• Consequence: UBAP2 NM_001370062.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.679
• Publications: 1 publications found

Genes affected

UBAP2 (HGNC:14185): (ubiquitin associated protein 2) The protein encoded by this gene contains a UBA (ubiquitin associated) domain, which is characteristic of proteins that function in the ubiquitination pathway. This gene may show increased expression in the adrenal gland and lymphatic tissues. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

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=0.09132767).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370062.2. 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
	UBAP2	NM_001370062.2	MANE Select	c.2761A>T	p.Met921Leu	missense	Exon 24 of 29	NP_001356991.2	Q5T6F2-1
	UBAP2	NM_001370059.2		c.2761A>T	p.Met921Leu	missense	Exon 24 of 29	NP_001356988.2	Q5T6F2-1
	UBAP2	NM_018449.4		c.2761A>T	p.Met921Leu	missense	Exon 24 of 29	NP_060919.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBAP2	ENST00000379238.7	TSL:5 MANE Select	c.2761A>T	p.Met921Leu	missense	Exon 24 of 29	ENSP00000368540.2	Q5T6F2-1
	UBAP2	ENST00000379235.5	TSL:1	n.1429A>T		non_coding_transcript_exon	Exon 5 of 10
	UBAP2	ENST00000862381.1		c.2884A>T	p.Met962Leu	missense	Exon 25 of 30	ENSP00000532440.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000477 AC: 12 AN: 251476 AF XY: 0.0000441

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000527

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.0000410 AC: 60 AN: 1461880 Hom.: 0 Cov.: 32 AF XY: 0.0000399 AC XY: 29 AN XY: 727242

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.000179 AC: 8 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000450 AC: 50 AN: 1112004

Other (OTH) AF: 0.0000331 AC: 2 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000675 Hom.: 0

Bravo AF: 0.00000756

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.0000330 AC: 4

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	0.14
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	9.3
DANN	Benign	0.61
DEOGEN2	Benign	0.029	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.68
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.069
Sift	Benign	0.70	T
Sift4G	Benign	0.46	T
Polyphen		0.0020	B
Vest4		0.30
MutPred		0.29		Gain of catalytic residue at M921 (P = 0.0651)
MVP		0.15
MPC		0.062
ClinPred		0.014	T
GERP RS		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.067
gMVP		0.24
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs771487841; hg19: chr9-33923828;