rs307658

Variant names:

• chr9-33941761-T-C
• rs307658
• NM_001370062.2:c.1817A>G

Variant summary

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

The NM_001370062.2(UBAP2):​c.1817A>G​(p.Asn606Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 1,613,590 control chromosomes in the GnomAD database, including 120,041 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.40 (12457 hom., cov: 31)
  • Exomes 𝑓: 0.38 (107584 hom.)
• Consequence: UBAP2 NM_001370062.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.76

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0011149049).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBAP2	NM_001370062.2	c.1817A>G	p.Asn606Ser	missense_variant	Exon 16 of 29	ENST00000379238.7	NP_001356991.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBAP2	ENST00000379238.7	c.1817A>G	p.Asn606Ser	missense_variant	Exon 16 of 29	5	NM_001370062.2	ENSP00000368540.2

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60486 AN: 151862 Hom.: 12430 Cov.: 31

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.367

GnomAD3 exomes AF: 0.364 AC: 91425 AN: 251426 Hom.: 17848 AF XY: 0.372 AC XY: 50568 AN XY: 135878

Gnomad AFR exome AF: 0.479

Gnomad AMR exome AF: 0.228

Gnomad ASJ exome AF: 0.299

Gnomad EAS exome AF: 0.164

Gnomad SAS exome AF: 0.477

Gnomad FIN exome AF: 0.447

Gnomad NFE exome AF: 0.380

Gnomad OTH exome AF: 0.371

GnomAD4 exome AF: 0.379 AC: 554217 AN: 1461610 Hom.: 107584 Cov.: 38 AF XY: 0.383 AC XY: 278130 AN XY: 727112

Gnomad4 AFR exome AF: 0.480

Gnomad4 AMR exome AF: 0.238

Gnomad4 ASJ exome AF: 0.297

Gnomad4 EAS exome AF: 0.225

Gnomad4 SAS exome AF: 0.480

Gnomad4 FIN exome AF: 0.445

Gnomad4 NFE exome AF: 0.379

Gnomad4 OTH exome AF: 0.372

GnomAD4 genome AF: 0.398 AC: 60561 AN: 151980 Hom.: 12457 Cov.: 31 AF XY: 0.399 AC XY: 29606 AN XY: 74268

Gnomad4 AFR AF: 0.473

Gnomad4 AMR AF: 0.304

Gnomad4 ASJ AF: 0.284

Gnomad4 EAS AF: 0.186

Gnomad4 SAS AF: 0.478

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.385

Gnomad4 OTH AF: 0.367

Alfa AF: 0.371 Hom.: 27509

Bravo AF: 0.382

TwinsUK AF: 0.375 AC: 1390

ALSPAC AF: 0.369 AC: 1423

ESP6500AA AF: 0.468 AC: 2060

ESP6500EA AF: 0.383 AC: 3291

ExAC AF: 0.374 AC: 45406

Asia WGS AF: 0.350 AC: 1220 AN: 3478

EpiCase AF: 0.370

EpiControl AF: 0.368

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.9
DANN	Benign	0.13
DEOGEN2	Benign	0.012	T;T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.078	.;T
MetaRNN	Benign	0.0011	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-2.1	N;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.50	N;N
REVEL	Benign	0.11
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.020	B;B
Vest4		0.025
MPC		0.055
ClinPred		0.0040	T
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.022
gMVP		0.088

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: rs307658; hg19: chr9-33941759; COSMIC: COSV62545734; COSMIC: COSV62545734;