3-35759275-T-G

Variant names:

• chr3-35759275-T-G
• rs9311109
• NM_001385562.1:c.2137+15310T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001385562.1(ARPP21):​c.2137+15310T>G variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARPP21 NM_001385562.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.261
• Publications: 3 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARPP21	NM_001385562.1	MANE Select	c.2137+15310T>G		intron	N/A	NP_001372491.1
	ARPP21	NM_001385595.1		c.2140+15310T>G		intron	N/A	NP_001372524.1
	ARPP21	NM_001385490.1		c.2137+15310T>G		intron	N/A	NP_001372419.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARPP21	ENST00000684406.1	MANE Select	c.2137+15310T>G		intron	N/A	ENSP00000506922.1
	ARPP21	ENST00000187397.8	TSL:1	c.2032+15310T>G		intron	N/A	ENSP00000187397.4
	ARPP21	ENST00000444190.5	TSL:1	c.1975+15310T>G		intron	N/A	ENSP00000405276.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.88
DANN	Benign	0.56
PhyloP100		-0.26

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: rs9311109; hg19: chr3-35800767;