dbSNP rs573485318: UBAP1L:p.Arg343His (chr15-65093215-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001163692.2(UBAP1L):c.1028G>A(p.Arg343His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000278 in 1,546,352 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R343C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

UBAP1L
NM_001163692.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0580

Publications

4 publications found

Variant links:

Genes affected

UBAP1L (HGNC:40028): (ubiquitin associated protein 1 like) Predicted to enable ubiquitin binding activity. Predicted to be involved in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway. Predicted to be part of ESCRT I complex. [provided by Alliance of Genome Resources, Apr 2022]

UBAP1L Gene-Disease associations (from GenCC):

inherited retinal dystrophy
Inheritance: AR Classification: DEFINITIVE Submitted by: Ambry Genetics
retinal degeneration
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

UBAP1L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07562557).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001163692.2. 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
	UBAP1L	NM_001163692.2	MANE Select	c.1028G>A	p.Arg343His	missense	Exon 6 of 6	NP_001157164.1	F5GYI3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UBAP1L	ENST00000559089.6	TSL:1 MANE Select	c.1028G>A	p.Arg343His	missense	Exon 6 of 6	ENSP00000454012.1	F5GYI3
UBAP1L	ENST00000561387.1	TSL:1	n.7171G>A		non_coding_transcript_exon	Exon 2 of 2
UBAP1L	ENST00000907325.1		c.1028G>A	p.Arg343His	missense	Exon 5 of 5	ENSP00000577384.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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

GnomAD2 exomes

AF:

0.00000672

AC:

AN:

148904

AF XY:

0.0000126

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000431

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000287

AC:

AN:

1394118

Hom.:

Cov.:

AF XY:

0.0000320

AC XY:

AN XY:

687614

show subpopulations

African (AFR)

AF:

0.000414

AC:

AN:

31366

American (AMR)

AF:

0.0000287

AC:

AN:

34806

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25062

East Asian (EAS)

AF:

0.0000281

AC:

AN:

35596

South Asian (SAS)

AF:

0.0000380

AC:

AN:

78862

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48312

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4966

European-Non Finnish (NFE)

AF:

0.00000464

AC:

AN:

1077386

Other (OTH)

AF:

0.000294

AC:

AN:

57762

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

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

AF:

0.0000197

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41544

American (AMR)

AF:

0.00

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5140

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000264

Asia WGS

AF:

0.000866

AC:

AN:

3478

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

Benign

0.085

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.014

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.80

M_CAP

Benign

0.0092

MetaRNN

Benign

0.076

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

0.058

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.60

REVEL

Benign

0.015

Sift

Benign

0.41

Sift4G

Benign

0.37

Polyphen

0.22

Vest4

0.082

MVP

0.014

ClinPred

0.16

GERP RS

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.032

gMVP

0.19

Mutation Taster

=89/11

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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