X-27461023-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_207319.4(PPP4R3C):c.2274A>G(p.Glu758=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000336 in 512,499 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 66 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., 6 hem., cov: 22)
  • Exomes 𝑓: 0.00035 (0 hom. 60 hem.)
• Consequence: PPP4R3C NM_207319.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.18

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant X-27461023-T-C is Benign according to our data. Variant chrX-27461023-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2660211.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.18 with no splicing effect.
• BS2: High Hemizygotes in GnomAd at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP4R3C	NM_207319.4	c.2274A>G	p.Glu758=	synonymous_variant	1/1	ENST00000412172.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP4R3C	ENST00000412172.4	c.2274A>G	p.Glu758=	synonymous_variant	1/1		NM_207319.4	P1

Frequencies

GnomAD3 genomes AF: 0.000297 AC: 33 AN: 110966 Hom.: 0 Cov.: 22 AF XY: 0.000181 AC XY: 6 AN XY: 33150

Gnomad AFR AF: 0.0000983

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000290

Gnomad ASJ AF: 0.000756

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000393

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000377

Gnomad OTH AF: 0.000667

GnomAD3 exomes AF: 0.000392 AC: 39 AN: 99472 Hom.: 0 AF XY: 0.000462 AC XY: 17 AN XY: 36832

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000208

Gnomad ASJ exome AF: 0.000823

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000718

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000523

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.000346 AC: 139 AN: 401476 Hom.: 0 Cov.: 0 AF XY: 0.000403 AC XY: 60 AN XY: 148910

Gnomad4 AFR exome AF: 0.0000801

Gnomad4 AMR exome AF: 0.000296

Gnomad4 ASJ exome AF: 0.000614

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000106

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000368

Gnomad4 OTH exome AF: 0.000822

GnomAD4 genome AF: 0.000297 AC: 33 AN: 111023 Hom.: 0 Cov.: 22 AF XY: 0.000181 AC XY: 6 AN XY: 33217

Gnomad4 AFR AF: 0.0000981

Gnomad4 AMR AF: 0.000289

Gnomad4 ASJ AF: 0.000756

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000394

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000377

Gnomad4 OTH AF: 0.000658

Alfa AF: 0.000521 Hom.: 4

Bravo AF: 0.000208

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2022

PPP4R3C: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	3.1
Dann	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs750640410; hg19: chrX-27479140;