7-94910228-T-A

Position:

• chr7-94910228-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001166160.2(PPP1R9A):​c.115T>A​(p.Ser39Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00568 in 1,613,640 control chromosomes in the GnomAD database, including 475 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (248 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (227 hom.)
• Consequence: PPP1R9A NM_001166160.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.964

Genes affected

PPP1R9A (HGNC:14946): (protein phosphatase 1 regulatory subunit 9A) This gene is imprinted, and located in a cluster of imprinted genes on chromosome 7q12. This gene is transcribed in both neuronal and multiple embryonic tissues, and it is maternally expressed mainly in embryonic skeletal muscle tissues and biallelically expressed in other embryonic tissues. The protein encoded by this gene includes a PDZ domain and a sterile alpha motif (SAM). It is a regulatory subunit of protein phosphatase I, and controls actin cytoskeleton reorganization. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014253259).
• BP6: Variant 7-94910228-T-A is Benign according to our data. Variant chr7-94910228-T-A is described in ClinVar as [Benign]. Clinvar id is 776241.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP1R9A	NM_001166160.2	c.115T>A	p.Ser39Thr	missense_variant	2/20	ENST00000433360.6	NP_001159632.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP1R9A	ENST00000433360.6	c.115T>A	p.Ser39Thr	missense_variant	2/20	1	NM_001166160.2	ENSP00000405514

Frequencies

GnomAD3 genomes AF: 0.0303 AC: 4594 AN: 151704 Hom.: 246 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00945

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000368

Gnomad OTH AF: 0.0212

GnomAD3 exomes AF: 0.00809 AC: 2032 AN: 251294 Hom.: 97 AF XY: 0.00576 AC XY: 782 AN XY: 135826

Gnomad AFR exome AF: 0.110

Gnomad AMR exome AF: 0.00535

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000334

Gnomad OTH exome AF: 0.00342

GnomAD4 exome AF: 0.00312 AC: 4563 AN: 1461820 Hom.: 227 Cov.: 31 AF XY: 0.00265 AC XY: 1930 AN XY: 727198

Gnomad4 AFR exome AF: 0.110

Gnomad4 AMR exome AF: 0.00608

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000104

Gnomad4 FIN exome AF: 0.0000375

Gnomad4 NFE exome AF: 0.000181

Gnomad4 OTH exome AF: 0.00652

GnomAD4 genome AF: 0.0303 AC: 4602 AN: 151820 Hom.: 248 Cov.: 32 AF XY: 0.0284 AC XY: 2107 AN XY: 74184

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.00943

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000368

Gnomad4 OTH AF: 0.0210

Alfa AF: 0.00462 Hom.: 18

Bravo AF: 0.0342

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.101 AC: 444

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00988 AC: 1199

Asia WGS AF: 0.00866 AC: 30 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 15, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	19
DANN	Benign	0.92
DEOGEN2	Benign	0.023	T;.;T;.;T;T;.;.
Eigen	Benign	0.025
Eigen_PC	Benign	0.053
FATHMM_MKL	Benign	0.76	D
LIST_S2	Benign	0.82	T;T;T;.;T;.;T;T
MetaRNN	Benign	0.0014	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	.;L;L;L;.;L;L;L
MutationTaster	Benign	0.97	N;N;N;N;N;N
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.2	N;N;N;N;N;N;N;N
REVEL	Benign	0.033
Sift	Benign	0.28	T;D;D;D;T;D;D;D
Sift4G	Benign	0.37	T;T;T;T;T;T;T;T
Polyphen		0.36	.;.;B;.;.;B;.;.
Vest4		0.33, 0.25, 0.33, 0.25, 0.22, 0.34
MVP		0.44
MPC		0.22
ClinPred		0.0099	T
GERP RS		1.7
Varity_R		0.084
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs113253337; hg19: chr7-94539540;