chr6-30602634-G-A

Position:

• chr6-30602634-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000376511.7(PPP1R10):​c.2015C>T​(p.Pro672Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,444,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P672S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PPP1R10 ENST00000376511.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.53

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
• BP4: Computational evidence support a benign effect (MetaRNN=0.41242096).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP1R10	NM_002714.4	c.2015C>T	p.Pro672Leu	missense_variant	19/20	ENST00000376511.7	NP_002705.2
PPP1R10	NM_001376195.1	c.2015C>T	p.Pro672Leu	missense_variant	19/20		NP_001363124.1
PPP1R10	XM_011514722.2	c.2015C>T	p.Pro672Leu	missense_variant	20/21		XP_011513024.1
PPP1R10	NR_072994.2	n.2506C>T		non_coding_transcript_exon_variant	19/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP1R10	ENST00000376511.7	c.2015C>T	p.Pro672Leu	missense_variant	19/20	1	NM_002714.4	ENSP00000365694	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1444620 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 718080

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: 9.04e-7

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

May 03, 2023

The c.2015C>T (p.P672L) alteration is located in exon 19 (coding exon 17) of the PPP1R10 gene. This alteration results from a C to T substitution at nucleotide position 2015, causing the proline (P) at amino acid position 672 to be replaced by a leucine (L). 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	0.28
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	23
DANN	Benign	0.96
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.86	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.091
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.012	D
Polyphen		0.99	D
Vest4		0.50
MutPred		0.34		Loss of glycosylation at P672 (P = 0.0256);
MVP		0.33
MPC		0.38
ClinPred		0.72	D
GERP RS		4.5
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		4.1
Varity_R		0.094
gMVP		0.30

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: chr6-30570411;