Genetic Variant NM_019121.2:c.241A>C (chr19-45138552-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_019121.2(PPP1R37):c.241A>C(p.Lys81Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000137 in 1,383,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

PPP1R37
NM_019121.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.37

Publications

1 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14901596).

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.241A>C	p.Lys81Gln	missense	Exon 2 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.241A>C	p.Lys81Gln	missense	Exon 2 of 13	ENSP00000221462.3	O75864-1
PPP1R37	ENST00000945762.1		c.361A>C	p.Lys121Gln	missense	Exon 3 of 14	ENSP00000615821.1
PPP1R37	ENST00000872789.1		c.241A>C	p.Lys81Gln	missense	Exon 2 of 13	ENSP00000542848.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1383710

Hom.:

Cov.:

AF XY:

0.0000132

AC XY:

AN XY:

682812

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31588

American (AMR)

AF:

0.00

AC:

AN:

35696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25182

East Asian (EAS)

AF:

0.00

AC:

AN:

35734

South Asian (SAS)

AF:

0.00

AC:

AN:

79236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33888

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5690

European-Non Finnish (NFE)

AF:

0.0000121

AC:

AN:

1078798

Other (OTH)

AF:

0.000104

AC:

AN:

57898

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

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.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.0062

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.20

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.79

M_CAP

Benign

0.0082

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.41

PhyloP100

4.4

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.4

REVEL

Benign

0.057

Sift

Benign

0.15

Sift4G

Benign

0.18

Polyphen

0.037

Vest4

0.27

MutPred

0.71

Loss of ubiquitination at K81 (P = 0.0167)

MVP

0.22

ClinPred

0.39

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.30

Mutation Taster

=93/7

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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