rs765288398

Variant names:

• chr19-45145823-T-C
• rs765288398
• NM_019121.2:c.1767T>C
• PPP1R37 p.Pro589Pro

Your query was ambiguous. Multiple possible variants found:

• chr19-45145823-T-C
• chr19-45145823-T-A
• chr19-45145823-T-G

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.902
• Publications: 0 publications found

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]

MARK4 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

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.

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>C	p.Pro589Pro	synonymous	Exon 11 of 13	NP_061994.1	O75864-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R37	ENST00000221462.9	TSL:5 MANE Select	c.1767T>C	p.Pro589Pro	synonymous	Exon 11 of 13	ENSP00000221462.3	O75864-1
	PPP1R37	ENST00000422370.2	TSL:1	n.3689T>C		non_coding_transcript_exon	Exon 3 of 3
	PPP1R37	ENST00000945762.1		c.1887T>C	p.Pro629Pro	synonymous	Exon 12 of 14	ENSP00000615821.1

Frequencies

GnomAD3 genomes AF: 0.0736 AC: 2016 AN: 27374 Hom.: 0 Cov.: 0

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

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

⚠️ 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: 20 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.

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

⚠️ 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: 48 AN: 604

East Asian (EAS) AF: 0.0330 AC: 33 AN: 1000

South Asian (SAS) AF: 0.0571 AC: 46 AN: 806

European-Finnish (FIN) AF: 0.0731 AC: 138 AN: 1888

Middle Eastern (MID) AF: 0.0862 AC: 5 AN: 58

European-Non Finnish (NFE) AF: 0.0756 AC: 913 AN: 12080

Other (OTH) AF: 0.0596 AC: 26 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.

Alfa AF: 0.0424 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.096
DANN	Benign	0.27
PhyloP100		-0.90
Mutation Taster		=100/0	polymorphism

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.

Other links and lift over

dbSNP: rs765288398;

hg19: chr19-45649081;