Genetic Variant UBAP2:p.Phe1026Cys (chr9-33922874-A-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001370062.2(UBAP2):c.3077T>G(p.Phe1026Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000995 in 1,597,622 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00010 ( 2 hom. )

Consequence

UBAP2
NM_001370062.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.95

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.21312177).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBAP2	NM_001370062.2 link	c.3077T>G	p.Phe1026Cys	missense_variant	Exon 28 of 29	ENST00000379238.7	NP_001356991.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBAP2	ENST00000379238.7 link	c.3077T>G	p.Phe1026Cys	missense_variant	Exon 28 of 29	5	NM_001370062.2	ENSP00000368540.2		Q5T6F2-1

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000177

AC:

AN:

242786

Hom.:

AF XY:

0.000153

AC XY:

AN XY:

131100

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00387

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000172

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000182

Gnomad OTH exome

AF:

0.000171

GnomAD4 exome

AF:

0.000103

AC:

149

AN:

1445344

Hom.:

Cov.:

AF XY:

0.000110

AC XY:

AN XY:

716696

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00398

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000201

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000136

Gnomad4 OTH exome

AF:

0.000269

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152278

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000315

Hom.:

Bravo

AF:

0.0000831

ExAC

AF:

0.000115

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 31, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3077T>G (p.F1026C) alteration is located in exon 28 (coding exon 27) of the UBAP2 gene. This alteration results from a T to G substitution at nucleotide position 3077, causing the phenylalanine (F) at amino acid position 1026 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.68

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Pathogenic

0.22

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.24

.;T;T

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.93

D;.;D

M_CAP

Benign

0.080

MetaRNN

Benign

0.21

T;T;T

MetaSVM

Benign

-0.43

MutationAssessor

Uncertain

2.5

.;M;M

PrimateAI

Pathogenic

0.80

PROVEAN

Pathogenic

-6.7

.;D;D

REVEL

Uncertain

0.51

Sift

Pathogenic

0.0

.;D;D

Sift4G

Benign

0.094

T;D;D

Polyphen

1.0

.;D;D

Vest4

0.94

MVP

0.33

MPC

0.092

ClinPred

0.33

GERP RS

6.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.84

gMVP

0.60

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over