rs779348594

Variant names:

• chr15-52557216-C-A
• rs779348594
• NM_006628.6:c.52G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-52557216-C-A
• chr15-52557216-C-T

Variant summary

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

The NM_006628.6(ARPP19):​c.52G>T​(p.Glu18*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000694 in 1,441,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ARPP19 NM_006628.6 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.98
• Publications: 0 publications found

Genes affected

ARPP19 (HGNC:16967): (cAMP regulated phosphoprotein 19) The 19-kD cAMP-regulated phosphoprotein plays a role in regulating mitosis by inhibiting protein phosphatase-2A (PP2A; see MIM 176915) (summary by Gharbi-Ayachi et al., 2010 [PubMed 21164014]).[supplied by OMIM, Feb 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006628.6. 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
	ARPP19	NM_006628.6	MANE Select	c.52G>T	p.Glu18*	stop_gained	Exon 2 of 3	NP_006619.1	P56211-1
	ARPP19	NM_001306191.2		c.109G>T	p.Glu37*	stop_gained	Exon 5 of 6	NP_001293120.1	H3BMD8
	ARPP19	NM_001306196.2		c.109G>T	p.Glu37*	stop_gained	Exon 3 of 4	NP_001293125.1	H3BMD8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARPP19	ENST00000249822.9	TSL:1 MANE Select	c.52G>T	p.Glu18*	stop_gained	Exon 2 of 3	ENSP00000249822.4	P56211-1
	ARPP19	ENST00000566423.5	TSL:1	c.52G>T	p.Glu18*	stop_gained	Exon 3 of 4	ENSP00000455625.1	P56211-1
	ARPP19	ENST00000561971.1	TSL:3	c.109G>T	p.Glu37*	stop_gained	Exon 5 of 6	ENSP00000454341.1	H3BMD8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1441662 Hom.: 0 Cov.: 28 AF XY: 0.00000139 AC XY: 1 AN XY: 717900

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32684

American (AMR) AF: 0.00 AC: 0 AN: 43170

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25804

East Asian (EAS) AF: 0.00 AC: 0 AN: 39510

South Asian (SAS) AF: 0.00 AC: 0 AN: 84444

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52366

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5706

European-Non Finnish (NFE) AF: 9.11e-7 AC: 1 AN: 1098298

Other (OTH) AF: 0.00 AC: 0 AN: 59680

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.65
CADD	Pathogenic	41
DANN	Uncertain	1.0
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	1.0
FATHMM_MKL	Pathogenic	0.99	D
PhyloP100		4.0
Vest4		0.48
GERP RS		6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.34		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.34		Position offset: 6

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

Other links and lift over

dbSNP: rs779348594; hg19: chr15-52849413;