14-35087292-A-C

Variant names:

• chr14-35087292-A-C
• rs10483452
• NM_017917.4:c.1173+659T>G

Variant summary

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

The NM_017917.4(PPP2R3C):​c.1173+659T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,256 control chromosomes in the GnomAD database, including 3,956 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 0.21 (3956 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PPP2R3C NM_017917.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22
• Publications: 12 publications found

Genes affected

PPP2R3C (HGNC:17485): (protein phosphatase 2 regulatory subunit B''gamma) This gene encodes a regulatory subunit of the serine/threonine phosphatase, protein phosphatase 2. This protein is localized to both nuclear and cytoplasmic regions depending on cell cycle phase. Homozygous conditional knockout mice for this gene exhibit reduced numbers and impaired proliferation of immune system B cells. This protein may regulate the expression of the P-glycoprotein ATP-binding cassette transporter through its phosphatase activity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2015]

ENSG00000279434 (HGNC:):

FAM177A1 (HGNC:19829): (family with sequence similarity 177 member A1) This gene encodes a member of a conserved protein family. Alternative splicing results in multiple transcript variants. This gene is thought to be associated with susceptibility to juvenile idiopathic arthritis. [provided by RefSeq, Apr 2017]

FAM177A1 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017917.4. 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
	PPP2R3C	NM_017917.4	MANE Select	c.1173+659T>G		intron	N/A	NP_060387.2
	PPP2R3C	NM_001305155.2		c.843+659T>G		intron	N/A	NP_001292084.1
	PPP2R3C	NM_001305156.2		c.843+659T>G		intron	N/A	NP_001292085.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R3C	ENST00000261475.10	TSL:1 MANE Select	c.1173+659T>G		intron	N/A	ENSP00000261475.5
	PPP2R3C	ENST00000553273.5	TSL:1	n.*839+659T>G		intron	N/A	ENSP00000451075.1
	PPP2R3C	ENST00000557217.5	TSL:1	n.*976+659T>G		intron	N/A	ENSP00000452436.1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31615 AN: 152138 Hom.: 3960 Cov.: 33

Gnomad AFR AF: 0.0817

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.0698

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.234

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.208 AC: 31614 AN: 152256 Hom.: 3956 Cov.: 33 AF XY: 0.202 AC XY: 15074 AN XY: 74444

African (AFR) AF: 0.0815 AC: 3387 AN: 41570

American (AMR) AF: 0.208 AC: 3185 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1035 AN: 3468

East Asian (EAS) AF: 0.0697 AC: 362 AN: 5192

South Asian (SAS) AF: 0.146 AC: 704 AN: 4828

European-Finnish (FIN) AF: 0.241 AC: 2552 AN: 10594

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.287 AC: 19518 AN: 68010

Other (OTH) AF: 0.232 AC: 490 AN: 2112

Alfa AF: 0.257 Hom.: 2848

Bravo AF: 0.202

Asia WGS AF: 0.106 AC: 368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.0
DANN	Benign	0.47
PhyloP100		1.2
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: rs10483452; hg19: chr14-35556498;