19-45142095-C-T
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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
NM_019121.2 missense
Scores
2
8
9
Clinical Significance
Conservation
PhyloP100: 5.78
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]
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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 |
---|---|---|---|---|---|---|---|
PPP1R37 | NM_019121.2 | c.602C>T | p.Thr201Met | missense_variant | 6/13 | ENST00000221462.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PPP1R37 | ENST00000221462.9 | c.602C>T | p.Thr201Met | missense_variant | 6/13 | 5 | NM_019121.2 | P1 | |
PPP1R37 | ENST00000422370.2 | n.59C>T | non_coding_transcript_exon_variant | 2/3 | 1 | ||||
PPP1R37 | ENST00000544069.2 | c.458C>T | p.Thr153Met | missense_variant | 4/4 | 5 | |||
MARK4 | ENST00000587566.5 | c.-277+62718C>T | intron_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.000144 AC: 22AN: 152254Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000108 AC: 14AN: 129972Hom.: 0 AF XY: 0.000113 AC XY: 8AN XY: 70658
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GnomAD4 exome AF: 0.000267 AC: 368AN: 1378176Hom.: 0 Cov.: 32 AF XY: 0.000256 AC XY: 174AN XY: 679308
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GnomAD4 genome AF: 0.000144 AC: 22AN: 152254Hom.: 0 Cov.: 33 AF XY: 0.000175 AC XY: 13AN XY: 74374
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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 submitter | clinical testing | Ambry Genetics | May 11, 2022 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Benign
T;T
Vest4
MVP
ClinPred
T
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at