4-101347783-T-C

Position:

• chr4-101347783-T-C

Variant summary

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

The NR_033874.1(FLJ20021):​n.7T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 155,222 control chromosomes in the GnomAD database, including 17,278 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 0.44 (17112 hom., cov: 34)
  • Exomes 𝑓: 0.30 (166 hom.)
• Consequence: FLJ20021 NR_033874.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42

Genes affected

FLJ20021 (HGNC:):

PPP3CA (HGNC:9314): (protein phosphatase 3 catalytic subunit alpha) Enables several functions, including ATPase binding activity; calmodulin binding activity; and calmodulin-dependent protein phosphatase activity. Involved in several processes, including calcineurin-NFAT signaling cascade; peptidyl-serine dephosphorylation; and response to calcium ion. Located in several cellular components, including cytosol; dendritic spine; and nucleoplasm. Part of calcineurin complex. Colocalizes with cytoplasmic side of plasma membrane. Implicated in developmental and epileptic encephalopathy 91. Biomarker of focal segmental glomerulosclerosis and schizophrenia. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLJ20021	NR_033874.1	n.7T>C		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLJ20021	ENST00000529296.3	n.32T>C		non_coding_transcript_exon_variant	1/2	5
PPP3CA	ENST00000529324.5	c.-93+450A>G		intron_variant		3
FLJ20021	ENST00000527564.2	n.32T>C		non_coding_transcript_exon_variant	1/2	2
FLJ20021	ENST00000689482.1	n.8T>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66540 AN: 152018 Hom.: 17065 Cov.: 34

Gnomad AFR AF: 0.703

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.379

GnomAD4 exome AF: 0.304 AC: 937 AN: 3086 Hom.: 166 Cov.: 0 AF XY: 0.318 AC XY: 638 AN XY: 2008

Gnomad4 AFR exome AF: 0.789

Gnomad4 AMR exome AF: 0.367

Gnomad4 ASJ exome AF: 0.208

Gnomad4 EAS exome AF: 0.362

Gnomad4 SAS exome AF: 0.350

Gnomad4 FIN exome AF: 0.429

Gnomad4 NFE exome AF: 0.279

Gnomad4 OTH exome AF: 0.386

GnomAD4 genome AF: 0.438 AC: 66650 AN: 152136 Hom.: 17112 Cov.: 34 AF XY: 0.445 AC XY: 33103 AN XY: 74372

Gnomad4 AFR AF: 0.704

Gnomad4 AMR AF: 0.441

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.524

Gnomad4 SAS AF: 0.413

Gnomad4 FIN AF: 0.425

Gnomad4 NFE AF: 0.284

Gnomad4 OTH AF: 0.385

Alfa AF: 0.287 Hom.: 1205

Bravo AF: 0.453

Asia WGS AF: 0.520 AC: 1809 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.3
DANN	Benign	0.81

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2850328; hg19: chr4-102268940;