Genetic Variant UBTD2:p.Asp110Asn (chr5-172212207-C-T) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_152277.3(UBTD2):c.328G>A(p.Asp110Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,452,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

UBTD2
NM_152277.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.70

Publications

1 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.929

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152277.3. 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
	UBTD2	NM_152277.3	MANE Select	c.328G>A	p.Asp110Asn	missense	Exon 3 of 3	NP_689490.2	Q8WUN7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UBTD2	ENST00000393792.3	TSL:1 MANE Select	c.328G>A	p.Asp110Asn	missense	Exon 3 of 3	ENSP00000377381.2	Q8WUN7
UBTD2	ENST00000901620.1		c.445G>A	p.Asp149Asn	missense	Exon 4 of 4	ENSP00000571679.1
UBTD2	ENST00000901619.1		c.409G>A	p.Asp137Asn	missense	Exon 4 of 4	ENSP00000571678.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000804

AC:

AN:

248674

AF XY:

0.0000149

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000292

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000892

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1452812

Hom.:

Cov.:

AF XY:

0.00000416

AC XY:

AN XY:

720824

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33264

American (AMR)

AF:

0.0000226

AC:

AN:

44250

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25936

East Asian (EAS)

AF:

0.0000254

AC:

AN:

39444

South Asian (SAS)

AF:

0.00

AC:

AN:

85858

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53328

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5720

European-Non Finnish (NFE)

AF:

9.05e-7

AC:

AN:

1105056

Other (OTH)

AF:

0.00

AC:

AN:

59956

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Benign

-0.059

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.45

Eigen

Pathogenic

1.0

Eigen_PC

Pathogenic

0.93

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Pathogenic

1.0

M_CAP

Benign

0.049

MetaRNN

Pathogenic

0.93

MetaSVM

Benign

-0.34

MutationAssessor

Pathogenic

3.3

PhyloP100

7.7

PrimateAI

Pathogenic

0.87

PROVEAN

Pathogenic

-4.8

REVEL

Uncertain

0.51

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.95

MutPred

0.78

Gain of helix (P = 0.2294)

MVP

0.51

MPC

1.3

ClinPred

0.99

GERP RS

5.7

Varity_R

0.97

gMVP

0.89

Mutation Taster

=27/73

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over