6-30604080-T-C

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2 BP4_Moderate

The NM_002714.4(PPP1R10):c.1436A>G(p.Asn479Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000212 in 1,461,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: PPP1R10 NM_002714.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.24

Genes affected

PPP1R10 (HGNC:9284): (protein phosphatase 1 regulatory subunit 10) This gene encodes a protein phosphatase 1 binding protein. The encoded protein plays a role in many cellular processes including cell cycle progression, DNA repair and apoptosis by regulating the activity of protein phosphatase 1. This gene lies within the major histocompatibility complex class I region on chromosome 6, and alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Jul 2012]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PP2: Missense variant where missense usually causes diseases, PPP1R10
• BP4: Computational evidence support a benign effect (MetaRNN=0.13144928).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP1R10	NM_002714.4	c.1436A>G	p.Asn479Ser	missense_variant	14/20	ENST00000376511.7
PPP1R10	NM_001376195.1	c.1436A>G	p.Asn479Ser	missense_variant	14/20
PPP1R10	XM_011514722.2	c.1436A>G	p.Asn479Ser	missense_variant	15/21
PPP1R10	NR_072994.2	n.1927A>G		non_coding_transcript_exon_variant	14/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP1R10	ENST00000376511.7	c.1436A>G	p.Asn479Ser	missense_variant	14/20	1	NM_002714.4	P1
PPP1R10	ENST00000496955.1	n.133A>G		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000796 AC: 2 AN: 251134 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135726

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000212 AC: 31 AN: 1461848 Hom.: 0 Cov.: 33 AF XY: 0.0000289 AC XY: 21 AN XY: 727228

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000216

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 16, 2022

The c.1436A>G (p.N479S) alteration is located in exon 14 (coding exon 12) of the PPP1R10 gene. This alteration results from a A to G substitution at nucleotide position 1436, causing the asparagine (N) at amino acid position 479 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.52
Cadd	Benign	18
Dann	Benign	0.91
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.10
FATHMM_MKL	Benign	0.67	D
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	0.96	D
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.90	N
REVEL	Benign	0.062
Sift	Benign	0.20	T
Sift4G	Benign	0.096	T
Polyphen		0.057	B
Vest4		0.24
MutPred		0.33		Gain of phosphorylation at N479 (P = 0.0501);
MVP		0.30
MPC		0.94
ClinPred		0.24	T
GERP RS		4.7
Varity_R		0.16
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs773428483; hg19: chr6-30571857;