9-34017108-C-T

Position:

• chr9-34017108-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001370062.2(UBAP2):​c.41G>A​(p.Arg14Gln) variant causes a missense change. The variant allele was found at a frequency of 0.619 in 1,610,116 control chromosomes in the GnomAD database, including 311,513 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.60 (27877 hom., cov: 31)
  • Exomes 𝑓: 0.62 (283636 hom.)
• Consequence: UBAP2 NM_001370062.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.25

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]

UBAP2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.2650975E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBAP2	NM_001370062.2	c.41G>A	p.Arg14Gln	missense_variant	2/29	ENST00000379238.7	NP_001356991.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBAP2	ENST00000379238.7	c.41G>A	p.Arg14Gln	missense_variant	2/29	5	NM_001370062.2	ENSP00000368540.2

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91337 AN: 151730 Hom.: 27866 Cov.: 31

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.696

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.815

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.615

Gnomad OTH AF: 0.635

GnomAD3 exomes AF: 0.635 AC: 158071 AN: 248838 Hom.: 51501 AF XY: 0.627 AC XY: 84347 AN XY: 134562

Gnomad AFR exome AF: 0.521

Gnomad AMR exome AF: 0.771

Gnomad ASJ exome AF: 0.701

Gnomad EAS exome AF: 0.836

Gnomad SAS exome AF: 0.520

Gnomad FIN exome AF: 0.552

Gnomad NFE exome AF: 0.620

Gnomad OTH exome AF: 0.629

GnomAD4 exome AF: 0.621 AC: 905225 AN: 1458274 Hom.: 283636 Cov.: 45 AF XY: 0.617 AC XY: 447884 AN XY: 725406

Gnomad4 AFR exome AF: 0.519

Gnomad4 AMR exome AF: 0.762

Gnomad4 ASJ exome AF: 0.702

Gnomad4 EAS exome AF: 0.775

Gnomad4 SAS exome AF: 0.519

Gnomad4 FIN exome AF: 0.555

Gnomad4 NFE exome AF: 0.621

Gnomad4 OTH exome AF: 0.628

GnomAD4 genome AF: 0.602 AC: 91380 AN: 151842 Hom.: 27877 Cov.: 31 AF XY: 0.602 AC XY: 44645 AN XY: 74204

Gnomad4 AFR AF: 0.527

Gnomad4 AMR AF: 0.696

Gnomad4 ASJ AF: 0.715

Gnomad4 EAS AF: 0.815

Gnomad4 SAS AF: 0.523

Gnomad4 FIN AF: 0.568

Gnomad4 NFE AF: 0.615

Gnomad4 OTH AF: 0.634

Alfa AF: 0.626 Hom.: 50728

Bravo AF: 0.618

TwinsUK AF: 0.625 AC: 2318

ALSPAC AF: 0.632 AC: 2434

ESP6500AA AF: 0.533 AC: 2347

ESP6500EA AF: 0.617 AC: 5309

ExAC AF: 0.626 AC: 76003

Asia WGS AF: 0.648 AC: 2248 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;T;T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.68	.;T;T
MetaRNN	Benign	0.0000013	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;M;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.3	N;N;N
REVEL	Benign	0.14
Sift	Benign	0.20	T;T;T
Sift4G	Benign	0.082	T;T;T
Polyphen		0.90	P;P;.
Vest4		0.22
MPC		0.12
ClinPred		0.011	T
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.30

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

Publications

LitVar

Other links and lift over

dbSNP: rs1785506; hg19: chr9-34017106; COSMIC: COSV62545718;