dbSNP rs1003294870: UBAC2:p.Ser4Arg (chr13-99200918-A-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001144072.2(UBAC2):c.10A>C(p.Ser4Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000536 in 1,306,868 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 0.0000066 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000052 ( 0 hom. )

Consequence

UBAC2
NM_001144072.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.41

Publications

0 publications found

Variant links:

Genes affected

UBAC2 (HGNC:20486): (UBA domain containing 2) Involved in negative regulation of canonical Wnt signaling pathway and negative regulation of retrograde protein transport, ER to cytosol. Acts upstream of or within protein localization to endoplasmic reticulum. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

UBAC2 links:

UBAC2-AS1 (HGNC:42502): (UBAC2 antisense RNA 1)

UBAC2-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28694203).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144072.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UBAC2	NM_001144072.2	MANE Select	c.10A>C	p.Ser4Arg	missense	Exon 1 of 9	NP_001137544.1	Q8NBM4-1
UBAC2	NM_177967.4		c.-494A>C		5_prime_UTR	Exon 1 of 7	NP_808882.1	Q8NBM4-2
UBAC2	NR_026644.2		n.65A>C		non_coding_transcript_exon	Exon 1 of 9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UBAC2	ENST00000403766.8	TSL:2 MANE Select	c.10A>C	p.Ser4Arg	missense	Exon 1 of 9	ENSP00000383911.3	Q8NBM4-1
UBAC2	ENST00000961156.1		c.10A>C	p.Ser4Arg	missense	Exon 1 of 10	ENSP00000631215.1
UBAC2	ENST00000858721.1		c.10A>C	p.Ser4Arg	missense	Exon 1 of 10	ENSP00000528780.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000520

AC:

AN:

1154668

Hom.:

Cov.:

AF XY:

0.00000362

AC XY:

AN XY:

552828

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24646

American (AMR)

AF:

0.0000628

AC:

AN:

15928

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15114

East Asian (EAS)

AF:

0.00

AC:

AN:

29802

South Asian (SAS)

AF:

0.00

AC:

AN:

28718

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38320

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4626

European-Non Finnish (NFE)

AF:

0.00000420

AC:

AN:

951482

Other (OTH)

AF:

0.0000217

AC:

AN:

46032

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

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:

0.00000657

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41442

American (AMR)

AF:

0.0000654

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2094

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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

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

0.75

BayesDel_addAF

Benign

-0.031

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.070

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.87

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.29

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

PhyloP100

4.4

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.7

REVEL

Benign

0.11

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.010

Polyphen

0.92

Vest4

0.51

MutPred

0.29

Loss of glycosylation at S4 (P = 0.0062)

MVP

0.60

MPC

1.2

ClinPred

0.98

GERP RS

3.5

PromoterAI

0.059

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.35

gMVP

0.44

Mutation Taster

=56/44

polymorphism

(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