19-45142095-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_019121.2(PPP1R37):​c.602C>T​(p.Thr201Met) variant causes a missense change. The variant allele was found at a frequency of 0.000255 in 1,530,430 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: 𝑓 0.00014 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

PPP1R37
NM_019121.2 missense

Scores

2
8
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.78
Variant links:
Genes affected
PPP1R37 (HGNC:27607): (protein phosphatase 1 regulatory subunit 37) Predicted to enable protein phosphatase inhibitor activity. Predicted to be involved in negative regulation of catalytic activity. [provided by Alliance of Genome Resources, Apr 2022]
MARK4 (HGNC:13538): (microtubule affinity regulating kinase 4) This gene encodes a member of the microtubule affinity-regulating kinase family. These protein kinases phosphorylate microtubule-associated proteins and regulate the transition between stable and dynamic microtubules. The encoded protein is associated with the centrosome throughout mitosis and may be involved in cell cycle control. Expression of this gene is a potential marker for cancer, and the encoded protein may also play a role in Alzheimer's disease. Pseudogenes of this gene are located on both the short and long arm of chromosome 3. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.3081508).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PPP1R37NM_019121.2 linkuse as main transcriptc.602C>T p.Thr201Met missense_variant 6/13 ENST00000221462.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PPP1R37ENST00000221462.9 linkuse as main transcriptc.602C>T p.Thr201Met missense_variant 6/135 NM_019121.2 P1O75864-1
PPP1R37ENST00000422370.2 linkuse as main transcriptn.59C>T non_coding_transcript_exon_variant 2/31
PPP1R37ENST00000544069.2 linkuse as main transcriptc.458C>T p.Thr153Met missense_variant 4/45
MARK4ENST00000587566.5 linkuse as main transcriptc.-277+62718C>T intron_variant 5

Frequencies

GnomAD3 genomes
AF:
0.000144
AC:
22
AN:
152254
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000217
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.000191
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000108
AC:
14
AN:
129972
Hom.:
0
AF XY:
0.000113
AC XY:
8
AN XY:
70658
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000414
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000135
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000202
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000267
AC:
368
AN:
1378176
Hom.:
0
Cov.:
32
AF XY:
0.000256
AC XY:
174
AN XY:
679308
show subpopulations
Gnomad4 AFR exome
AF:
0.0000318
Gnomad4 AMR exome
AF:
0.0000848
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000761
Gnomad4 FIN exome
AF:
0.0000297
Gnomad4 NFE exome
AF:
0.000326
Gnomad4 OTH exome
AF:
0.000104
GnomAD4 genome
AF:
0.000144
AC:
22
AN:
152254
Hom.:
0
Cov.:
33
AF XY:
0.000175
AC XY:
13
AN XY:
74374
show subpopulations
Gnomad4 AFR
AF:
0.000217
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000191
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000208
Hom.:
0
Bravo
AF:
0.000106
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000519
AC:
2
ExAC
AF:
0.0000511
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 11, 2022The c.602C>T (p.T201M) alteration is located in exon 6 (coding exon 6) of the PPP1R37 gene. This alteration results from a C to T substitution at nucleotide position 602, causing the threonine (T) at amino acid position 201 to be replaced by a methionine (M). 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
0.24
BayesDel_addAF
Benign
-0.080
T
BayesDel_noAF
Uncertain
-0.070
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.095
T;T
Eigen
Uncertain
0.20
Eigen_PC
Uncertain
0.25
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.90
D;D
M_CAP
Uncertain
0.11
D
MetaRNN
Benign
0.31
T;T
MetaSVM
Benign
-0.79
T
MutationAssessor
Benign
1.8
L;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.81
D
PROVEAN
Uncertain
-3.9
D;D
REVEL
Benign
0.21
Sift
Uncertain
0.0070
D;D
Sift4G
Benign
0.076
T;T
Vest4
0.76
MVP
0.44
ClinPred
0.24
T
GERP RS
3.9
Varity_R
0.20
gMVP
0.61

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: rs766123136; hg19: chr19-45645353; COSMIC: COSV55523894; COSMIC: COSV55523894; API