3-35759275-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001385562.1(ARPP21):​c.2137+15310T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,100 control chromosomes in the GnomAD database, including 1,338 homozygotes. 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: 𝑓 0.13 (1338 hom., 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

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>C		intron	N/A	NP_001372491.1
	ARPP21	NM_001385595.1		c.2140+15310T>C		intron	N/A	NP_001372524.1
	ARPP21	NM_001385490.1		c.2137+15310T>C		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>C		intron	N/A	ENSP00000506922.1
	ARPP21	ENST00000187397.8	TSL:1	c.2032+15310T>C		intron	N/A	ENSP00000187397.4
	ARPP21	ENST00000444190.5	TSL:1	c.1975+15310T>C		intron	N/A	ENSP00000405276.1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19244 AN: 151982 Hom.: 1334 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.0955

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0688

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.127 AC: 19264 AN: 152100 Hom.: 1338 Cov.: 32 AF XY: 0.120 AC XY: 8950 AN XY: 74352

African (AFR) AF: 0.123 AC: 5108 AN: 41526

American (AMR) AF: 0.0954 AC: 1457 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 406 AN: 3464

East Asian (EAS) AF: 0.00136 AC: 7 AN: 5156

South Asian (SAS) AF: 0.130 AC: 629 AN: 4822

European-Finnish (FIN) AF: 0.0688 AC: 729 AN: 10600

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.153 AC: 10417 AN: 67946

Other (OTH) AF: 0.137 AC: 290 AN: 2114

Alfa AF: 0.130 Hom.: 289

Bravo AF: 0.128

Asia WGS AF: 0.0570 AC: 199 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.0
DANN	Benign	0.56
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

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;