rs765288398

Positions:

• chr19-45145823-T-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_019121.2(PPP1R37):​c.1767T>C​(p.Pro589=) 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.902

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]

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
PPP1R37	NM_019121.2	c.1767T>C	p.Pro589=	synonymous_variant	11/13	ENST00000221462.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP1R37	ENST00000221462.9	c.1767T>C	p.Pro589=	synonymous_variant	11/13	5	NM_019121.2	P1
PPP1R37	ENST00000422370.2	n.3689T>C		non_coding_transcript_exon_variant	3/3	1
MARK4	ENST00000587566.5	c.-277+66446T>C		intron_variant		5
PPP1R37	ENST00000540059.1	n.692T>C		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 2016 AN: 27374 Hom.: 0 Cov.: 0 FAILED QC

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

GnomAD3 exomes AF: 0.163 AC: 4440 AN: 27294 Hom.: 6 AF XY: 0.172 AC XY: 2476 AN XY: 14356

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 SAS exome AF: 0.282

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.: 7 Cov.: 4 AF XY: 0.0539 AC XY: 5045 AN XY: 93546

Gnomad4 AFR exome AF: 0.0339

Gnomad4 AMR exome AF: 0.142

Gnomad4 ASJ exome AF: 0.0560

Gnomad4 EAS exome AF: 0.0431

Gnomad4 SAS exome AF: 0.103

Gnomad4 FIN exome AF: 0.0864

Gnomad4 NFE exome AF: 0.0333

Gnomad4 OTH exome AF: 0.0508

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0736 AC: 2017 AN: 27400 Hom.: 0 Cov.: 0 AF XY: 0.0737 AC XY: 991 AN XY: 13452

Gnomad4 AFR AF: 0.0799

Gnomad4 AMR AF: 0.0698

Gnomad4 ASJ AF: 0.0795

Gnomad4 EAS AF: 0.0330

Gnomad4 SAS AF: 0.0571

Gnomad4 FIN AF: 0.0731

Gnomad4 NFE AF: 0.0756

Gnomad4 OTH AF: 0.0596

Alfa AF: 0.0424 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

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
DANN	Benign	0.27

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

LitVar

Other links and lift over

dbSNP: rs765288398; hg19: chr19-45649081;