chr7-94910915-A-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001166160.2(PPP1R9A):​c.802A>T​(p.Thr268Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000165 in 1,614,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00092 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000087 ( 0 hom. )

Consequence

PPP1R9A
NM_001166160.2 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.846
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0049404204).
BP6
Variant 7-94910915-A-T is Benign according to our data. Variant chr7-94910915-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 2657686.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PPP1R9ANM_001166160.2 linkuse as main transcriptc.802A>T p.Thr268Ser missense_variant 2/20 ENST00000433360.6 NP_001159632.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PPP1R9AENST00000433360.6 linkuse as main transcriptc.802A>T p.Thr268Ser missense_variant 2/201 NM_001166160.2 ENSP00000405514 Q9ULJ8-3

Frequencies

GnomAD3 genomes
AF:
0.000920
AC:
140
AN:
152218
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00321
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000327
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:
0.00
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.000235
AC:
59
AN:
250834
Hom.:
0
AF XY:
0.000170
AC XY:
23
AN XY:
135602
show subpopulations
Gnomad AFR exome
AF:
0.00339
Gnomad AMR exome
AF:
0.0000579
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:
0.00
Gnomad OTH exome
AF:
0.000327
GnomAD4 exome
AF:
0.0000869
AC:
127
AN:
1461812
Hom.:
0
Cov.:
31
AF XY:
0.0000715
AC XY:
52
AN XY:
727196
show subpopulations
Gnomad4 AFR exome
AF:
0.00329
Gnomad4 AMR exome
AF:
0.0000894
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:
0.000166
GnomAD4 genome
AF:
0.000919
AC:
140
AN:
152336
Hom.:
0
Cov.:
32
AF XY:
0.000913
AC XY:
68
AN XY:
74514
show subpopulations
Gnomad4 AFR
AF:
0.00320
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.0000727
Hom.:
0
Bravo
AF:
0.000895
ESP6500AA
AF:
0.00318
AC:
14
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000264
AC:
32
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenMay 01, 2022PPP1R9A: BP4 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.077
BayesDel_addAF
Benign
-0.44
T
BayesDel_noAF
Benign
-0.41
CADD
Benign
6.0
DANN
Benign
0.43
DEOGEN2
Benign
0.026
.;T;.;T;.;.
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.12
N
LIST_S2
Benign
0.65
T;T;.;.;T;T
M_CAP
Benign
0.053
D
MetaRNN
Benign
0.0049
T;T;T;T;T;T
MetaSVM
Benign
-0.71
T
MutationAssessor
Benign
0.90
L;L;L;L;L;L
MutationTaster
Benign
1.0
N;N;N;N;N;N
PrimateAI
Benign
0.23
T
PROVEAN
Benign
0.22
N;N;N;N;N;N
REVEL
Benign
0.25
Sift
Benign
0.10
T;D;T;D;T;T
Sift4G
Benign
0.74
T;T;T;T;T;T
Polyphen
0.0
.;B;.;B;.;.
Vest4
0.043
MVP
0.40
MPC
0.15
ClinPred
0.010
T
GERP RS
-2.5
Varity_R
0.050
gMVP
0.12

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs138552151; hg19: chr7-94540227; API