chr2-68188635-G-A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_000945.4(PPP3R1):​c.99C>T​(p.Asp33=) variant causes a synonymous change. The variant allele was found at a frequency of 0.429 in 1,611,810 control chromosomes in the GnomAD database, including 152,011 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16010 hom., cov: 31)
Exomes 𝑓: 0.43 ( 136001 hom. )

Consequence

PPP3R1
NM_000945.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.12
Variant links:
Genes affected
PPP3R1 (HGNC:9317): (protein phosphatase 3 regulatory subunit B, alpha) Enables cyclosporin A binding activity; phosphatase binding activity; and protein domain specific binding activity. Involved in calcineurin-NFAT signaling cascade and positive regulation of transcription by RNA polymerase II. Part of calcineurin complex. Implicated in Alzheimer's disease and dilated cardiomyopathy. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
Variant 2-68188635-G-A is Benign according to our data. Variant chr2-68188635-G-A is described in ClinVar as [Benign]. Clinvar id is 1181494.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PPP3R1NM_000945.4 linkuse as main transcriptc.99C>T p.Asp33= synonymous_variant 3/6 ENST00000234310.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PPP3R1ENST00000234310.8 linkuse as main transcriptc.99C>T p.Asp33= synonymous_variant 3/61 NM_000945.4 P1
PPP3R1ENST00000409752.5 linkuse as main transcriptc.156C>T p.Asp52= synonymous_variant 3/63
PPP3R1ENST00000409377.1 linkuse as main transcriptc.69C>T p.Asp23= synonymous_variant 3/63

Frequencies

GnomAD3 genomes
AF:
0.455
AC:
69109
AN:
151774
Hom.:
15994
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.492
Gnomad AMI
AF:
0.292
Gnomad AMR
AF:
0.478
Gnomad ASJ
AF:
0.460
Gnomad EAS
AF:
0.506
Gnomad SAS
AF:
0.618
Gnomad FIN
AF:
0.538
Gnomad MID
AF:
0.551
Gnomad NFE
AF:
0.401
Gnomad OTH
AF:
0.473
GnomAD3 exomes
AF:
0.473
AC:
117015
AN:
247438
Hom.:
28599
AF XY:
0.480
AC XY:
64440
AN XY:
134372
show subpopulations
Gnomad AFR exome
AF:
0.493
Gnomad AMR exome
AF:
0.471
Gnomad ASJ exome
AF:
0.461
Gnomad EAS exome
AF:
0.514
Gnomad SAS exome
AF:
0.635
Gnomad FIN exome
AF:
0.538
Gnomad NFE exome
AF:
0.408
Gnomad OTH exome
AF:
0.481
GnomAD4 exome
AF:
0.426
AC:
621984
AN:
1459918
Hom.:
136001
Cov.:
37
AF XY:
0.432
AC XY:
314112
AN XY:
726282
show subpopulations
Gnomad4 AFR exome
AF:
0.497
Gnomad4 AMR exome
AF:
0.471
Gnomad4 ASJ exome
AF:
0.458
Gnomad4 EAS exome
AF:
0.475
Gnomad4 SAS exome
AF:
0.632
Gnomad4 FIN exome
AF:
0.535
Gnomad4 NFE exome
AF:
0.397
Gnomad4 OTH exome
AF:
0.447
GnomAD4 genome
AF:
0.455
AC:
69174
AN:
151892
Hom.:
16010
Cov.:
31
AF XY:
0.464
AC XY:
34425
AN XY:
74238
show subpopulations
Gnomad4 AFR
AF:
0.492
Gnomad4 AMR
AF:
0.477
Gnomad4 ASJ
AF:
0.460
Gnomad4 EAS
AF:
0.506
Gnomad4 SAS
AF:
0.618
Gnomad4 FIN
AF:
0.538
Gnomad4 NFE
AF:
0.401
Gnomad4 OTH
AF:
0.478
Alfa
AF:
0.421
Hom.:
8959
Bravo
AF:
0.447
Asia WGS
AF:
0.586
AC:
2032
AN:
3472
EpiCase
AF:
0.418
EpiControl
AF:
0.411

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxJun 15, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.46
CADD
Benign
11
DANN
Benign
0.64

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: rs687; hg19: chr2-68415767; COSMIC: COSV52246314; API