3-35687748-C-G

Variant names:

• chr3-35687748-C-G
• rs2081055067
• NM_001385562.1:c.271C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001385562.1(ARPP21):​c.271C>G​(p.His91Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 5.43
• Publications: 0 publications found

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

ACMG classification

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=0.2552418).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARPP21	NM_001385562.1	MANE Select	c.271C>G	p.His91Asp	missense	Exon 6 of 21	NP_001372491.1	A0A804HI65
	ARPP21	NM_001385595.1		c.271C>G	p.His91Asp	missense	Exon 6 of 21	NP_001372524.1
	ARPP21	NM_001385490.1		c.271C>G	p.His91Asp	missense	Exon 6 of 21	NP_001372419.1	A0A804HI65

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARPP21	ENST00000684406.1	MANE Select	c.271C>G	p.His91Asp	missense	Exon 6 of 21	ENSP00000506922.1	A0A804HI65
	ARPP21	ENST00000187397.8	TSL:1	c.271C>G	p.His91Asp	missense	Exon 6 of 20	ENSP00000187397.4	Q9UBL0-1
	ARPP21	ENST00000444190.5	TSL:1	c.271C>G	p.His91Asp	missense	Exon 6 of 19	ENSP00000405276.1	Q9UBL0-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000468 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		5.4
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.20
Sift	Uncertain	0.024	D
Sift4G	Uncertain	0.048	D
Polyphen		0.48	P
Vest4		0.56
MutPred		0.21		Gain of glycosylation at S89 (P = 0.0043)
MVP		0.41
ClinPred		0.85	D
GERP RS		5.8
Varity_R		0.25
gMVP		0.28
Mutation Taster		=79/21	polymorphism

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

Other links and lift over

dbSNP: rs2081055067; hg19: chr3-35729240;