19-45145823-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_019121.2(PPP1R37):c.1767T>C(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. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.074 ( 0 hom., cov: 0)

Exomes 𝑓: 0.045 ( 7 hom. )

Failed GnomAD Quality Control

Consequence

PPP1R37
NM_019121.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

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: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 19-45145823-T-C is Benign according to our data. Variant chr19-45145823-T-C is described in ClinVar as Benign. ClinVar VariationId is 403337.Status of the report is criteria_provided_single_submitter, 1 stars.

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>C	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>C	p.Pro589Pro	synonymous_variant	Exon 11 of 13	5	NM_019121.2	ENSP00000221462.3	O75864-1
PPP1R37	ENST00000422370.2 link	n.3689T>C		non_coding_transcript_exon_variant	Exon 3 of 3	1
PPP1R37	ENST00000540059.1 link	n.692T>C		non_coding_transcript_exon_variant	Exon 1 of 3	2
MARK4	ENST00000587566.5 link	c.-277+66446T>C		intron_variant	Intron 1 of 6	5		ENSP00000465414.1	K7EK17

Frequencies

GnomAD3 genomes

AF:

0.0736

AC:

2016

AN:

27374

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0800

Gnomad AMI

AF:

0.0820

Gnomad AMR

AF:

0.0696

Gnomad ASJ

AF:

0.0795

Gnomad EAS

AF:

0.0329

Gnomad SAS

AF:

0.0591

Gnomad FIN

AF:

0.0731

Gnomad MID

AF:

0.0833

Gnomad NFE

AF:

0.0756

Gnomad OTH

AF:

0.0602

GnomAD2 exomes

AF:

0.163

AC:

4440

AN:

27294

AF XY:

0.172

show subpopulations

Gnomad AFR exome

AF:

0.0638

Gnomad AMR exome

AF:

0.200

Gnomad ASJ exome

AF:

0.226

Gnomad EAS exome

AF:

0.0961

Gnomad FIN exome

AF:

0.303

Gnomad NFE exome

AF:

0.123

Gnomad OTH exome

AF:

0.142

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0455

AC:

8408

AN:

184942

Hom.:

Cov.:

AF XY:

0.0539

AC XY:

5045

AN XY:

93546

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0339

AC:

136

AN:

4006

American (AMR)

AF:

0.142

AC:

673

AN:

4740

Ashkenazi Jewish (ASJ)

AF:

0.0560

AC:

157

AN:

2802

East Asian (EAS)

AF:

0.0431

AC:

191

AN:

4428

South Asian (SAS)

AF:

0.103

AC:

1865

AN:

18114

European-Finnish (FIN)

AF:

0.0864

AC:

368

AN:

4258

Middle Eastern (MID)

AF:

0.0394

AC:

AN:

508

European-Non Finnish (NFE)

AF:

0.0333

AC:

4600

AN:

138248

Other (OTH)

AF:

0.0508

AC:

398

AN:

7838

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.323

Heterozygous variant carriers

720

1440

2159

2879

3599

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0736

AC:

2017

AN:

27400

Hom.:

Cov.:

AF XY:

0.0737

AC XY:

991

AN XY:

13452

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0799

AC:

565

AN:

7068

American (AMR)

AF:

0.0698

AC:

233

AN:

3338

Ashkenazi Jewish (ASJ)

AF:

0.0795

AC:

AN:

604

East Asian (EAS)

AF:

0.0330

AC:

AN:

1000

South Asian (SAS)

AF:

0.0571

AC:

AN:

806

European-Finnish (FIN)

AF:

0.0731

AC:

138

AN:

1888

Middle Eastern (MID)

AF:

0.0862

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0756

AC:

913

AN:

12080

Other (OTH)

AF:

0.0596

AC:

AN:

436

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.278

Heterozygous variant carriers

191

382

572

763

954

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0424

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.096

(source)

DANN

Benign

0.27

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over