chr20-59939085-C-T

Variant names:

• chr20-59939085-C-T
• rs774974410
• NM_006242.4:c.847G>A

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.847G>A​(p.Ala283Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000245 in 1,589,330 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000026 (0 hom.)
• Consequence: PPP1R3D NM_006242.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.05
• 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=0.07940748).

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.847G>A	p.Ala283Thr	missense	Exon 1 of 1	NP_006233.1	O95685
	FAM217B	NM_001190826.2		c.-203+973C>T		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.847G>A	p.Ala283Thr	missense	Exon 1 of 1	ENSP00000360035.3	O95685
	FAM217B	ENST00000358293.7	TSL:2	c.-203+973C>T		intron	N/A	ENSP00000351040.3	Q9NTX9
	FAM217B	ENST00000890684.1		c.-203+973C>T		intron	N/A	ENSP00000560743.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151992 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000171 AC: 4 AN: 233982 AF XY: 0.0000313

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000366

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000264 AC: 38 AN: 1437338 Hom.: 0 Cov.: 31 AF XY: 0.0000322 AC XY: 23 AN XY: 714044

African (AFR) AF: 0.0000306 AC: 1 AN: 32666

American (AMR) AF: 0.00 AC: 0 AN: 42220

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25478

East Asian (EAS) AF: 0.00 AC: 0 AN: 39176

South Asian (SAS) AF: 0.00 AC: 0 AN: 85446

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43664

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5672

European-Non Finnish (NFE) AF: 0.0000299 AC: 33 AN: 1103434

Other (OTH) AF: 0.0000671 AC: 4 AN: 59582

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151992 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74242

African (AFR) AF: 0.00 AC: 0 AN: 41366

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67998

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000103 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		2.1
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.018
Sift	Benign	0.49	T
Sift4G	Benign	0.67	T
Polyphen		0.11	B
Vest4		0.044
MutPred		0.28		Loss of sheet (P = 0.1158)
MVP		0.68
MPC		0.79
ClinPred		0.16	T
GERP RS		3.0
Varity_R		0.050
gMVP		0.35
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: rs774974410; hg19: chr20-58514140;