Genetic Variant UBTD2:p.Arg180Gln (chr5-172211996-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_152277.3(UBTD2):c.539G>A(p.Arg180Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000991 in 1,614,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

UBTD2
NM_152277.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.09

Variant links:

Genes affected

UBTD2 (HGNC:24463): (ubiquitin domain containing 2) Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

UBTD2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33403748).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBTD2	NM_152277.3 link	c.539G>A	p.Arg180Gln	missense_variant	Exon 3 of 3	ENST00000393792.3	NP_689490.2	Q8WUN7B3KMW8
UBTD2	XM_017010022.2 link	c.407G>A	p.Arg136Gln	missense_variant	Exon 3 of 3		XP_016865511.1	Q8WUN7B2R886
UBTD2	XM_047417875.1 link	c.407G>A	p.Arg136Gln	missense_variant	Exon 3 of 3		XP_047273831.1
UBTD2	XM_047417876.1 link	c.407G>A	p.Arg136Gln	missense_variant	Exon 4 of 4		XP_047273832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBTD2	ENST00000393792.3 link	c.539G>A	p.Arg180Gln	missense_variant	Exon 3 of 3	1	NM_152277.3	ENSP00000377381.2		Q8WUN7

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251388

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000453

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 13, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.539G>A (p.R180Q) alteration is located in exon 3 (coding exon 3) of the UBTD2 gene. This alteration results from a G to A substitution at nucleotide position 539, causing the arginine (R) at amino acid position 180 to be replaced by a glutamine (Q). 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

Benign

0.091

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.031

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.81

M_CAP

Benign

0.029

MetaRNN

Benign

0.33

MetaSVM

Benign

-0.55

MutationAssessor

Benign

1.1

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-1.6

REVEL

Uncertain

0.30

Sift

Benign

0.53

Sift4G

Benign

0.72

Polyphen

0.99

Vest4

0.27

MVP

0.49

MPC

1.4

ClinPred

0.31

GERP RS

6.0

Varity_R

0.16

gMVP

0.49

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