Genetic Variant ARPP21:p.Ala179Thr (chr3-35690130-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001385562.1(ARPP21):c.535G>A(p.Ala179Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ARPP21
NM_001385562.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.08

Publications

0 publications found

Variant links:

Genes affected

ARPP21 (HGNC:16968): (cAMP regulated phosphoprotein 21) This gene encodes a cAMP-regulated phosphoprotein. The encoded protein is enriched in the caudate nucleus and cerebellar cortex. A similar protein in mouse may be involved in regulating the effects of dopamine in the basal ganglia. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]

ARPP21 Gene-Disease associations (from GenCC):

amyotrophic lateral sclerosis
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ARPP21 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09151322).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385562.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARPP21	NM_001385562.1	MANE Select	c.535G>A	p.Ala179Thr	missense	Exon 8 of 21	NP_001372491.1	A0A804HI65
ARPP21	NM_001385595.1		c.535G>A	p.Ala179Thr	missense	Exon 8 of 21	NP_001372524.1
ARPP21	NM_001385490.1		c.535G>A	p.Ala179Thr	missense	Exon 8 of 21	NP_001372419.1	A0A804HI65

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARPP21	ENST00000684406.1	MANE Select	c.535G>A	p.Ala179Thr	missense	Exon 8 of 21	ENSP00000506922.1	A0A804HI65
ARPP21	ENST00000187397.8	TSL:1	c.535G>A	p.Ala179Thr	missense	Exon 8 of 20	ENSP00000187397.4	Q9UBL0-1
ARPP21	ENST00000444190.5	TSL:1	c.535G>A	p.Ala179Thr	missense	Exon 8 of 19	ENSP00000405276.1	Q9UBL0-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1308328

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

659530

African (AFR)

AF:

0.00

AC:

AN:

30384

American (AMR)

AF:

0.00

AC:

AN:

44156

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24944

East Asian (EAS)

AF:

0.00

AC:

AN:

38758

South Asian (SAS)

AF:

0.00

AC:

AN:

82704

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53152

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5438

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

973724

Other (OTH)

AF:

0.00

AC:

AN:

55068

GnomAD4 genome

Cov.:

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

0.071

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.052

Eigen

Benign

0.019

Eigen_PC

Benign

0.081

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.011

MetaRNN

Benign

0.092

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.66

PhyloP100

3.1

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.040

REVEL

Benign

0.076

Sift

Benign

0.34

Sift4G

Benign

0.43

Polyphen

0.0010

Vest4

0.13

MutPred

0.50

Loss of catalytic residue at A179 (P = 0.0359)

MVP

0.44

ClinPred

0.61

GERP RS

3.9

PromoterAI

-0.0030

Neutral

(source)

Varity_R

0.063

gMVP

0.21

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over