chr3-35687797-G-A

Position:

• chr3-35687797-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001385562.1(ARPP21):​c.320G>A​(p.Arg107Lys) 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. 14/21 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)
• Consequence: ARPP21 NM_001385562.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.31

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]

ACMG classification

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=0.095077604).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARPP21	NM_001385562.1	c.320G>A	p.Arg107Lys	missense_variant	6/21	ENST00000684406.1	NP_001372491.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARPP21	ENST00000684406.1	c.320G>A	p.Arg107Lys	missense_variant	6/21		NM_001385562.1	ENSP00000506922	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2023

ARPP21: PM2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Uncertain	23
DANN	Benign	0.96
DEOGEN2	Benign	0.037	.;T;.
Eigen	Benign	0.039
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.85	D;T;T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.095	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;L;L
MutationTaster	Benign	0.96	N;N;N;N;N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.17	N;N;N
REVEL	Benign	0.037
Sift	Benign	0.56	T;T;T
Sift4G	Benign	0.57	T;T;T
Polyphen		0.29	B;B;B
Vest4		0.23
MutPred		0.27		Gain of glycosylation at S111 (P = 0);Gain of glycosylation at S111 (P = 0);Gain of glycosylation at S111 (P = 0);
MVP		0.26
ClinPred		0.39	T
GERP RS		5.7
Varity_R		0.15
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-35729289;