chr19-45093360-C-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_019121.2(PPP1R37):c.35C>G(p.Pro12Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000148 in 1,355,694 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P12L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

PPP1R37
NM_019121.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.11

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: G2P

MARK4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27338493).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019121.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R37	NM_019121.2	MANE Select	c.35C>G	p.Pro12Arg	missense	Exon 1 of 13	NP_061994.1	O75864-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PPP1R37	ENST00000221462.9	TSL:5 MANE Select	c.35C>G	p.Pro12Arg	missense	Exon 1 of 13	ENSP00000221462.3	O75864-1
PPP1R37	ENST00000945762.1		c.35C>G	p.Pro12Arg	missense	Exon 1 of 14	ENSP00000615821.1
PPP1R37	ENST00000872789.1		c.35C>G	p.Pro12Arg	missense	Exon 1 of 13	ENSP00000542848.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000886

AC:

AN:

112926

AF XY:

0.0000160

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000236

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000148

AC:

AN:

1355694

Hom.:

Cov.:

AF XY:

0.00000300

AC XY:

AN XY:

666486

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28862

American (AMR)

AF:

0.00

AC:

AN:

33332

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24412

East Asian (EAS)

AF:

0.00

AC:

AN:

33604

South Asian (SAS)

AF:

0.00

AC:

AN:

77004

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33202

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5360

European-Non Finnish (NFE)

AF:

0.00000188

AC:

AN:

1063466

Other (OTH)

AF:

0.00

AC:

AN:

56452

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0055

Eigen

Benign

0.081

Eigen_PC

Benign

0.10

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.50

M_CAP

Pathogenic

0.39

MetaRNN

Benign

0.27

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.69

PhyloP100

1.1

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.85

REVEL

Benign

0.095

Sift

Benign

0.040

Sift4G

Uncertain

0.0020

Polyphen

0.93

Vest4

0.12

MutPred

0.16

Gain of methylation at P12 (P = 0.0354)

MVP

0.43

ClinPred

0.41

GERP RS

3.0

PromoterAI

-0.10

Neutral

(source)

Varity_R

0.10

gMVP

0.31

Mutation Taster

=89/11

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over