NM_017917.4:c.1174-10dupT

Variant names:

• chr14-35085787-G-GA
• rs201794373
• NM_017917.4:c.1174-10dupT

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The NM_017917.4(PPP2R3C):​c.1174-10dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00115 in 1,537,448 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0026 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00099 (2 hom.)
• Consequence: PPP2R3C NM_017917.4 intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.0310
• Publications: 0 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]

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

LOC101927178 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP6: Variant 14-35085787-G-GA is Benign according to our data. Variant chr14-35085787-G-GA is described in ClinVar as Benign. ClinVar VariationId is 3039479.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00259 (390/150464) while in subpopulation AFR AF = 0.00872 (358/41064). AF 95% confidence interval is 0.00797. There are 2 homozygotes in GnomAd4. There are 172 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AD,AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R3C	NM_017917.4	MANE Select	c.1174-10dupT		intron	N/A	NP_060387.2
	PPP2R3C	NM_001305155.2		c.844-10dupT		intron	N/A	NP_001292084.1	Q969Q6-2
	PPP2R3C	NM_001305156.2		c.844-10dupT		intron	N/A	NP_001292085.1	Q969Q6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R3C	ENST00000261475.10	TSL:1 MANE Select	c.1174-10_1174-9insT		intron	N/A	ENSP00000261475.5	Q969Q6-1
	PPP2R3C	ENST00000553273.5	TSL:1	n.*840-10_*840-9insT		intron	N/A	ENSP00000451075.1	G3V228
	PPP2R3C	ENST00000557217.5	TSL:1	n.*977-10_*977-9insT		intron	N/A	ENSP00000452436.1	G3V228

Frequencies

GnomAD3 genomes AF: 0.00259 AC: 390 AN: 150352 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00874

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00139

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000968

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000592

Gnomad OTH AF: 0.000970

GnomAD2 exomes AF: 0.00241 AC: 431 AN: 179080 AF XY: 0.00229

Gnomad AFR exome AF: 0.0111

Gnomad AMR exome AF: 0.00261

Gnomad ASJ exome AF: 0.00259

Gnomad EAS exome AF: 0.00165

Gnomad FIN exome AF: 0.00263

Gnomad NFE exome AF: 0.00126

Gnomad OTH exome AF: 0.000952

GnomAD4 exome AF: 0.000989 AC: 1372 AN: 1386984 Hom.: 2 Cov.: 29 AF XY: 0.000920 AC XY: 635 AN XY: 690408

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

African (AFR) AF: 0.00900 AC: 273 AN: 30350

American (AMR) AF: 0.00163 AC: 59 AN: 36240

Ashkenazi Jewish (ASJ) AF: 0.000662 AC: 16 AN: 24170

East Asian (EAS) AF: 0.000598 AC: 23 AN: 38446

South Asian (SAS) AF: 0.00107 AC: 84 AN: 78626

European-Finnish (FIN) AF: 0.00106 AC: 53 AN: 50060

Middle Eastern (MID) AF: 0.000548 AC: 3 AN: 5476

European-Non Finnish (NFE) AF: 0.000745 AC: 795 AN: 1066426

Other (OTH) AF: 0.00115 AC: 66 AN: 57190

⚠️ 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 AF: 0.00259 AC: 390 AN: 150464 Hom.: 2 Cov.: 32 AF XY: 0.00234 AC XY: 172 AN XY: 73396

African (AFR) AF: 0.00872 AC: 358 AN: 41064

American (AMR) AF: 0.00139 AC: 21 AN: 15106

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3456

East Asian (EAS) AF: 0.000970 AC: 5 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4780

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10102

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000592 AC: 4 AN: 67518

Other (OTH) AF: 0.000960 AC: 2 AN: 2084

Alfa AF: 0.00477 Hom.: 0

Bravo AF: 0.00288

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PPP2R3C-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.031
Mutation Taster		=100/0	polymorphism

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: rs201794373; hg19: chr14-35554993;