Variant 3-35682850-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001385562.1(ARPP21):c.132G>T(p.Arg44Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000373 in 1,607,668 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ARPP21
NM_001385562.1 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.39

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 links:

ARPP21 (HGNC:):

ARPP21 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2520645).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARPP21	NM_001385562.1 linkuse as main transcript	c.132G>T	p.Arg44Ser	missense_variant, splice_region_variant	4/21	ENST00000684406.1	NP_001372491.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARPP21	ENST00000684406.1 linkuse as main transcript	c.132G>T	p.Arg44Ser	missense_variant, splice_region_variant	4/21		NM_001385562.1	ENSP00000506922.1		A0A804HI65

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151564

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1456104

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724510

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151564

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73984

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000295

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 15, 2024

The c.132G>T (p.R44S) alteration is located in exon 4 (coding exon 2) of the ARPP21 gene. This alteration results from a G to T substitution at nucleotide position 132, causing the arginine (R) at amino acid position 44 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.52

BayesDel_addAF

Benign

-0.082

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

T;.;.;.;T;.;T;.;.;.;.;.;T;T;.;.;.;.;.

Eigen

Benign

0.071

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.95

D;.;D;D;D;D;D;.;.;.;.;.;D;D;D;.;.;.;D

M_CAP

Benign

0.035

MetaRNN

Benign

0.25

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.80

MutationAssessor

Uncertain

2.3

.;M;M;.;M;.;.;M;M;M;M;M;.;.;M;M;M;M;M

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-4.2

D;D;N;D;N;D;D;D;D;D;D;D;D;D;N;D;D;D;D

REVEL

Benign

0.066

Sift

Uncertain

0.014

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

Sift4G

Benign

0.074

T;D;D;D;D;D;T;D;D;D;D;D;D;T;D;D;D;D;D

Polyphen

0.82, 0.73

.;.;P;.;P;.;.;.;.;.;.;.;.;.;P;.;.;.;.

Vest4

0.30, 0.24, 0.25, 0.23, 0.41

MutPred

0.25

Loss of MoRF binding (P = 0.0653);Loss of MoRF binding (P = 0.0653);Loss of MoRF binding (P = 0.0653);Loss of MoRF binding (P = 0.0653);Loss of MoRF binding (P = 0.0653);Loss of MoRF binding (P = 0.0653);Loss of MoRF binding (P = 0.0653);Loss of MoRF binding (P = 0.0653);Loss of MoRF binding (P = 0.0653);Loss of MoRF binding (P = 0.0653);Loss of MoRF binding (P = 0.0653);Loss of MoRF binding (P = 0.0653);Loss of MoRF binding (P = 0.0653);Loss of MoRF binding (P = 0.0653);Loss of MoRF binding (P = 0.0653);Loss of MoRF binding (P = 0.0653);Loss of MoRF binding (P = 0.0653);Loss of MoRF binding (P = 0.0653);Loss of MoRF binding (P = 0.0653);

MVP

0.61

ClinPred

0.97

GERP RS

3.3

Varity_R

0.23

gMVP

0.35

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over