NM_017917.4:c.1173+677A>G

Variant names:

• chr14-35087274-T-C
• rs17103033
• NM_017917.4:c.1173+677A>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+677A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,242 control chromosomes in the GnomAD database, including 1,980 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 0.15 (1980 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PPP2R3C NM_017917.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.125
• Publications: 10 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R3C	NM_017917.4	c.1173+677A>G		intron_variant	Intron 12 of 12	ENST00000261475.10	NP_060387.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R3C	ENST00000261475.10	c.1173+677A>G		intron_variant	Intron 12 of 12	1	NM_017917.4	ENSP00000261475.5

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23440 AN: 152124 Hom.: 1981 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.0725

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.0452

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.0748

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.151

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

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: 0.154 AC: 23451 AN: 152242 Hom.: 1980 Cov.: 32 AF XY: 0.150 AC XY: 11138 AN XY: 74448

African (AFR) AF: 0.209 AC: 8664 AN: 41526

American (AMR) AF: 0.117 AC: 1781 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 403 AN: 3470

East Asian (EAS) AF: 0.0453 AC: 235 AN: 5192

South Asian (SAS) AF: 0.177 AC: 854 AN: 4826

European-Finnish (FIN) AF: 0.0748 AC: 793 AN: 10604

Middle Eastern (MID) AF: 0.216 AC: 63 AN: 292

European-Non Finnish (NFE) AF: 0.151 AC: 10276 AN: 68024

Other (OTH) AF: 0.150 AC: 316 AN: 2112

Alfa AF: 0.141 Hom.: 952

Bravo AF: 0.159

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.8
DANN	Benign	0.47
PhyloP100		0.13
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: rs17103033; hg19: chr14-35556480;