6-30601655-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_002714.4(PPP1R10):c.2717T>C(p.Met906Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,584 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PPP1R10 NM_002714.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.05

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, PPP1R10
• BP4: Computational evidence support a benign effect (MetaRNN=0.25680876).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP1R10	NM_002714.4	c.2717T>C	p.Met906Thr	missense_variant	20/20	ENST00000376511.7
PPP1R10	NM_001376195.1	c.2717T>C	p.Met906Thr	missense_variant	20/20
PPP1R10	XM_011514722.2	c.2717T>C	p.Met906Thr	missense_variant	21/21
PPP1R10	NR_072994.2	n.3208T>C		non_coding_transcript_exon_variant	20/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP1R10	ENST00000376511.7	c.2717T>C	p.Met906Thr	missense_variant	20/20	1	NM_002714.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461584 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727120

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Jun 29, 2023

The c.2717T>C (p.M906T) alteration is located in exon 20 (coding exon 18) of the PPP1R10 gene. This alteration results from a T to C substitution at nucleotide position 2717, causing the methionine (M) at amino acid position 906 to be replaced by a threonine (T). 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	Uncertain	0.40
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Benign	-0.30
Cadd	Uncertain	24
Dann	Benign	0.84
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
MutationTaster	Benign	0.92	D
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.82	N
REVEL	Benign	0.22
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.019	D
Polyphen		0.010	B
Vest4		0.60
MutPred		0.26		Gain of catalytic residue at M906 (P = 0.0415);
MVP		0.36
MPC		1.6
ClinPred		0.52	D
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.41
gMVP		0.69

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-30569432;