Genetic Variant PPP1R37:p.Pro589Pro (chr19-45145823-T-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP7

The NM_019121.2(PPP1R37):c.1767T>A(p.Pro589Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P589P) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PPP1R37
NM_019121.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.902

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

new If you want to explore the variant's impact on the transcript NM_019121.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP7

Synonymous conserved (PhyloP=-0.902 with no splicing effect.

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.1767T>A	p.Pro589Pro	synonymous	Exon 11 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.1767T>A	p.Pro589Pro	synonymous	Exon 11 of 13	ENSP00000221462.3	O75864-1
PPP1R37	ENST00000422370.2	TSL:1	n.3689T>A		non_coding_transcript_exon	Exon 3 of 3
PPP1R37	ENST00000945762.1		c.1887T>A	p.Pro629Pro	synonymous	Exon 12 of 14	ENSP00000615821.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

32788

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

215900

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

109892

African (AFR)

AF:

0.00

AC:

AN:

4512

American (AMR)

AF:

0.00

AC:

AN:

5810

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3448

East Asian (EAS)

AF:

0.00

AC:

AN:

5348

South Asian (SAS)

AF:

0.00

AC:

AN:

22512

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5406

Middle Eastern (MID)

AF:

0.00

AC:

AN:

622

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

158890

Other (OTH)

AF:

0.00

AC:

AN:

9352

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

32818

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

16148

African (AFR)

AF:

0.00

AC:

AN:

8452

American (AMR)

AF:

0.00

AC:

AN:

4052

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

740

East Asian (EAS)

AF:

0.00

AC:

AN:

1124

South Asian (SAS)

AF:

0.00

AC:

AN:

936

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2208

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

14578

Other (OTH)

AF:

0.00

AC:

AN:

508

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.083

(source)

DANN

Benign

0.45

PhyloP100

-0.90

Mutation Taster

=100/0

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over