Variant 19-45093471-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_019121.2(PPP1R37):c.146C>G(p.Pro49Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000795 in 1,383,266 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000080 ( 0 hom. )

Consequence

PPP1R37
NM_019121.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.61

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]

PPP1R37 links:

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]

MARK4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.755

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP1R37	NM_019121.2 linkuse as main transcript	c.146C>G	p.Pro49Arg	missense_variant	1/13	ENST00000221462.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP1R37	ENST00000221462.9 linkuse as main transcript	c.146C>G	p.Pro49Arg	missense_variant	1/13	5	NM_019121.2	P1	O75864-1
PPP1R37	ENST00000544069.2 linkuse as main transcript	c.146C>G	p.Pro49Arg	missense_variant	1/4	5
MARK4	ENST00000587566.5 linkuse as main transcript	c.-277+14094C>G		intron_variant		5
PPP1R37	ENST00000496125.2 linkuse as main transcript	n.267C>G		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000741

AC:

AN:

134996

Hom.:

AF XY:

0.0000136

AC XY:

AN XY:

73574

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000191

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000795

AC:

AN:

1383266

Hom.:

Cov.:

AF XY:

0.00000879

AC XY:

AN XY:

682540

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000318

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000278

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Apr 22, 2022

The c.146C>G (p.P49R) alteration is located in exon 1 (coding exon 1) of the PPP1R37 gene. This alteration results from a C to G substitution at nucleotide position 146, causing the proline (P) at amino acid position 49 to be replaced by an arginine (R). 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

Pathogenic

0.98

BayesDel_addAF

Uncertain

0.060

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

T;T

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.76

T;T

M_CAP

Pathogenic

0.66

MetaRNN

Pathogenic

0.76

D;D

MetaSVM

Uncertain

0.22

MutationAssessor

Benign

0.69

N;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.94

PROVEAN

Pathogenic

-6.9

D;D

REVEL

Uncertain

0.53

Sift

Uncertain

0.0030

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.50

MutPred

0.35

Gain of MoRF binding (P = 9e-04);Gain of MoRF binding (P = 9e-04);

MVP

0.55

ClinPred

0.90

GERP RS

4.0

Varity_R

0.59

gMVP

0.65

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over