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

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R37	NM_019121.2 link	c.1767T>A	p.Pro589Pro	synonymous_variant	Exon 11 of 13	ENST00000221462.9	NP_061994.1	O75864-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PPP1R37	ENST00000221462.9 link	c.1767T>A	p.Pro589Pro	synonymous_variant	Exon 11 of 13	5	NM_019121.2	ENSP00000221462.3	O75864-1
PPP1R37	ENST00000422370.2 link	n.3689T>A		non_coding_transcript_exon_variant	Exon 3 of 3	1
PPP1R37	ENST00000540059.1 link	n.692T>A		non_coding_transcript_exon_variant	Exon 1 of 3	2
MARK4	ENST00000587566.5 link	c.-277+66446T>A		intron_variant	Intron 1 of 6	5		ENSP00000465414.1	K7EK17

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 v4.3

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over