rs12842916

Positions:

• chrX-27461222-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_207319.4(PPP4R3C):​c.2075T>C​(p.Val692Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 109,705 control chromosomes in the GnomAD database, including 12,789 homozygotes. There are 17,402 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 6/9 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.53 (12789 hom., 17402 hem., cov: 22)
  • Exomes 𝑓: 0.66 (54939 hom. 99394 hem.)
  • Failed GnomAD Quality Control
• Consequence: PPP4R3C NM_207319.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.62

Genes affected

PPP4R3C (HGNC:33146): (protein phosphatase 4 regulatory subunit 3C)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.2172288E-6).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP4R3C	NM_207319.4	c.2075T>C	p.Val692Ala	missense_variant	1/1	ENST00000412172.4	NP_997202.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP4R3C	ENST00000412172.4	c.2075T>C	p.Val692Ala	missense_variant	1/1		NM_207319.4	ENSP00000489770	P1

Frequencies

GnomAD3 genomes AF: 0.535 AC: 58674 AN: 109652 Hom.: 12785 Cov.: 22 AF XY: 0.544 AC XY: 17390 AN XY: 31990

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.762

Gnomad FIN AF: 0.664

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.555

GnomAD3 exomes AF: 0.650 AC: 64994 AN: 99917 Hom.: 13424 AF XY: 0.667 AC XY: 24710 AN XY: 37051

Gnomad AFR exome AF: 0.177

Gnomad AMR exome AF: 0.673

Gnomad ASJ exome AF: 0.608

Gnomad EAS exome AF: 0.591

Gnomad SAS exome AF: 0.765

Gnomad FIN exome AF: 0.677

Gnomad NFE exome AF: 0.677

Gnomad OTH exome AF: 0.632

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.657 AC: 263860 AN: 401587 Hom.: 54939 Cov.: 0 AF XY: 0.667 AC XY: 99394 AN XY: 149015

Gnomad4 AFR exome AF: 0.198

Gnomad4 AMR exome AF: 0.672

Gnomad4 ASJ exome AF: 0.614

Gnomad4 EAS exome AF: 0.600

Gnomad4 SAS exome AF: 0.762

Gnomad4 FIN exome AF: 0.673

Gnomad4 NFE exome AF: 0.675

Gnomad4 OTH exome AF: 0.615

GnomAD4 genome AF: 0.535 AC: 58685 AN: 109705 Hom.: 12789 Cov.: 22 AF XY: 0.543 AC XY: 17402 AN XY: 32053

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.632

Gnomad4 ASJ AF: 0.626

Gnomad4 EAS AF: 0.589

Gnomad4 SAS AF: 0.763

Gnomad4 FIN AF: 0.664

Gnomad4 NFE AF: 0.675

Gnomad4 OTH AF: 0.559

Alfa AF: 0.642 Hom.: 22013

Bravo AF: 0.516

TwinsUK AF: 0.706 AC: 2618

ALSPAC AF: 0.704 AC: 2035

ExAC AF: 0.602 AC: 9986

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.0080
DANN	Benign	0.69
FATHMM_MKL	Benign	0.0034	N
LIST_S2	Benign	0.061	T
MetaRNN	Benign	0.0000012	T
GERP RS		-0.34
Varity_R		0.052
gMVP		0.058

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12842916; hg19: chrX-27479339; COSMIC: COSV69080725;