dbSNP rs753912517: UBTD1:p.Leu102Val (chr10-97570143-C-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_024954.5(UBTD1):c.304C>G(p.Leu102Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000689 in 1,450,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L102F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

UBTD1
NM_024954.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.95

Publications

0 publications found

Variant links:

Genes affected

UBTD1 (HGNC:25683): (ubiquitin domain containing 1) The degradation of many proteins is carried out by the ubiquitin pathway in which proteins are targeted for degradation by covalent conjugation of the polypeptide ubiquitin. This gene encodes a protein that belongs to the ubiquitin family of proteins. The encoded protein is thought to regulate E2 ubiquitin conjugating enzymes belonging to the UBE2D family. [provided by RefSeq, Mar 2014]

UBTD1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.745

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024954.5. 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
	UBTD1	NM_024954.5	MANE Select	c.304C>G	p.Leu102Val	missense	Exon 3 of 3	NP_079230.1	Q9HAC8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UBTD1	ENST00000370664.4	TSL:1 MANE Select	c.304C>G	p.Leu102Val	missense	Exon 3 of 3	ENSP00000359698.3	Q9HAC8
UBTD1	ENST00000958439.1		c.397C>G	p.Leu133Val	missense	Exon 4 of 4	ENSP00000628498.1
UBTD1	ENST00000923989.1		c.76C>G	p.Leu26Val	missense	Exon 2 of 2	ENSP00000594048.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1450808

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719656

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33298

American (AMR)

AF:

0.00

AC:

AN:

44506

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25914

East Asian (EAS)

AF:

0.00

AC:

AN:

39426

South Asian (SAS)

AF:

0.00

AC:

AN:

85942

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51878

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

9.06e-7

AC:

AN:

1104270

Other (OTH)

AF:

0.00

AC:

AN:

59850

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.17

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.063

MetaRNN

Pathogenic

0.75

MetaSVM

Uncertain

0.0056

MutationAssessor

Pathogenic

3.4

PhyloP100

4.9

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-2.9

REVEL

Uncertain

0.33

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0030

Polyphen

0.80

Vest4

0.81

MutPred

0.37

Loss of helix (P = 0.079)

MVP

0.52

MPC

1.1

ClinPred

0.99

GERP RS

4.1

Varity_R

0.68

gMVP

0.79

Mutation Taster

=44/56

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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