rs12842916

Variant names:

• chrX-27461222-A-G
• rs12842916
• NM_207319.4:c.2075T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PPP4R3C	NM_207319.4	c.2075T>C	p.Val692Ala	missense_variant	Exon 1 of 1	ENST00000412172.4	NP_997202.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP4R3C	ENST00000412172.4	c.2075T>C	p.Val692Ala	missense_variant	Exon 1 of 1	6	NM_207319.4	ENSP00000489770.1

Frequencies

GnomAD3 genomes AF: 0.535 AC: 58674 AN: 109652 Hom.: 12785 Cov.: 22

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

GnomAD2 exomes AF: 0.650 AC: 64994 AN: 99917 AF XY: 0.667

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 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

African (AFR) AF: 0.198 AC: 2480 AN: 12500

American (AMR) AF: 0.672 AC: 18198 AN: 27086

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 9008 AN: 14663

East Asian (EAS) AF: 0.600 AC: 14470 AN: 24108

South Asian (SAS) AF: 0.762 AC: 28851 AN: 37873

European-Finnish (FIN) AF: 0.673 AC: 17262 AN: 25648

Middle Eastern (MID) AF: 0.556 AC: 1658 AN: 2983

European-Non Finnish (NFE) AF: 0.675 AC: 157694 AN: 233587

Other (OTH) AF: 0.615 AC: 14239 AN: 23139

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

African (AFR) AF: 0.201 AC: 6103 AN: 30344

American (AMR) AF: 0.632 AC: 6460 AN: 10226

Ashkenazi Jewish (ASJ) AF: 0.626 AC: 1641 AN: 2620

East Asian (EAS) AF: 0.589 AC: 2019 AN: 3425

South Asian (SAS) AF: 0.763 AC: 1886 AN: 2472

European-Finnish (FIN) AF: 0.664 AC: 3789 AN: 5703

Middle Eastern (MID) AF: 0.483 AC: 101 AN: 209

European-Non Finnish (NFE) AF: 0.675 AC: 35489 AN: 52552

Other (OTH) AF: 0.559 AC: 830 AN: 1486

Alfa AF: 0.589 Hom.: 25200

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
PhyloP100		-3.6
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

Other links and lift over

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