rs781129324

Variant names:

• chr20-59939670-C-A
• rs781129324
• NM_006242.4:c.262G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-59939670-C-A
• chr20-59939670-C-G
• chr20-59939670-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006242.4(PPP1R3D):​c.262G>T​(p.Ala88Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000763 in 1,310,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A88T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: PPP1R3D NM_006242.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.302
• Publications: 0 publications found

Genes affected

PPP1R3D (HGNC:9294): (protein phosphatase 1 regulatory subunit 3D) Phosphorylation of serine and threonine residues in proteins is a crucial step in the regulation of many cellular functions ranging from hormonal regulation to cell division and even short-term memory. The level of phosphorylation is controlled by the opposing actions of protein kinases and protein phosphatases. Protein phosphatase 1 (PP1) is 1 of 4 major serine/threonine-specific protein phosphatases which have been identified in eukaryotic cells. PP1 associates with various regulatory subunits that dictate its subcellular localization and modulate its substrate specificity. Several subunits that target PP1 to glycogen have been identified. This gene encodes a glycogen-targeting subunit of PP1. [provided by RefSeq, Jul 2008]

FAM217B (HGNC:16170): (family with sequence similarity 217 member B) Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0875113).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006242.4. 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
	PPP1R3D	NM_006242.4	MANE Select	c.262G>T	p.Ala88Ser	missense	Exon 1 of 1	NP_006233.1	O95685
	FAM217B	NM_001190826.2		c.-203+1558C>A		intron	N/A	NP_001177755.1	Q9NTX9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R3D	ENST00000370996.5	TSL:6 MANE Select	c.262G>T	p.Ala88Ser	missense	Exon 1 of 1	ENSP00000360035.3	O95685
	FAM217B	ENST00000358293.7	TSL:2	c.-203+1558C>A		intron	N/A	ENSP00000351040.3	Q9NTX9
	FAM217B	ENST00000890684.1		c.-203+1558C>A		intron	N/A	ENSP00000560743.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.63e-7 AC: 1 AN: 1310848 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 643436

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

African (AFR) AF: 0.00 AC: 0 AN: 26514

American (AMR) AF: 0.00 AC: 0 AN: 23350

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20982

East Asian (EAS) AF: 0.00 AC: 0 AN: 30732

South Asian (SAS) AF: 0.00 AC: 0 AN: 67468

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36728

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4736

European-Non Finnish (NFE) AF: 9.56e-7 AC: 1 AN: 1045822

Other (OTH) AF: 0.00 AC: 0 AN: 54516

⚠️ 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 Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	14
DANN	Benign	0.93
DEOGEN2	Benign	0.0075	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.30
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.062
Sift	Benign	0.083	T
Sift4G	Benign	0.21	T
Polyphen		0.010	B
Vest4		0.098
MutPred		0.31		Gain of phosphorylation at A88 (P = 0.0092)
MVP		0.51
MPC		0.78
ClinPred		0.063	T
GERP RS		2.3
Varity_R		0.063
gMVP		0.24
Mutation Taster		=92/8	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: rs781129324; hg19: chr20-58514725;