Variant 3-35681854-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001385562.1(ARPP21):c.103G>T(p.Asp35Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,190 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ARPP21
NM_001385562.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.88

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARPP21	NM_001385562.1 linkuse as main transcript	c.103G>T	p.Asp35Tyr	missense_variant	3/21	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.103G>T	p.Asp35Tyr	missense_variant	3/21		NM_001385562.1	ENSP00000506922	P4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

250164

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135194

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000887

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460190

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726402

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:

0.00

GnomAD4 genome

Cov.:

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

Sep 22, 2023

The c.103G>T (p.D35Y) alteration is located in exon 3 (coding exon 1) of the ARPP21 gene. This alteration results from a G to T substitution at nucleotide position 103, causing the aspartic acid (D) at amino acid position 35 to be replaced by a tyrosine (Y). 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

Benign

0.17

BayesDel_addAF

Uncertain

0.057

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

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

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.84

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

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

M_CAP

Benign

0.021

MetaRNN

Uncertain

0.43

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

MetaSVM

Benign

-0.50

MutationAssessor

Uncertain

2.1

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

MutationTaster

Benign

1.0

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

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-7.4

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

REVEL

Benign

0.28

Sift

Uncertain

0.0010

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

Sift4G

Pathogenic

0.0010

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

Polyphen

1.0

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

Vest4

0.37, 0.27, 0.28, 0.30, 0.35, 0.36

MutPred

0.15

Gain of glycosylation at S33 (P = 0.0014);Gain of glycosylation at S33 (P = 0.0014);Gain of glycosylation at S33 (P = 0.0014);Gain of glycosylation at S33 (P = 0.0014);Gain of glycosylation at S33 (P = 0.0014);Gain of glycosylation at S33 (P = 0.0014);Gain of glycosylation at S33 (P = 0.0014);Gain of glycosylation at S33 (P = 0.0014);Gain of glycosylation at S33 (P = 0.0014);Gain of glycosylation at S33 (P = 0.0014);Gain of glycosylation at S33 (P = 0.0014);Gain of glycosylation at S33 (P = 0.0014);Gain of glycosylation at S33 (P = 0.0014);Gain of glycosylation at S33 (P = 0.0014);Gain of glycosylation at S33 (P = 0.0014);Gain of glycosylation at S33 (P = 0.0014);Gain of glycosylation at S33 (P = 0.0014);Gain of glycosylation at S33 (P = 0.0014);Gain of glycosylation at S33 (P = 0.0014);Gain of glycosylation at S33 (P = 0.0014);

MVP

0.81

ClinPred

1.0

GERP RS

6.0

Varity_R

0.57

gMVP

0.50

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

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