rs10421085

Variant names:

• chr19-45119364-A-G
• rs10421085
• NM_019121.2:c.203-19150A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000221462.9(PPP1R37):​c.203-19150A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0341 in 152,128 control chromosomes in the GnomAD database, including 301 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.034 (301 hom., cov: 32)
• Consequence: PPP1R37 ENST00000221462.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.502
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000221462.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R37	NM_019121.2	MANE Select	c.203-19150A>G		intron	N/A	NP_061994.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R37	ENST00000221462.9	TSL:5 MANE Select	c.203-19150A>G		intron	N/A	ENSP00000221462.3
	PPP1R37	ENST00000544069.2	TSL:5	c.203-21142A>G		intron	N/A	ENSP00000445252.1
	MARK4	ENST00000587566.5	TSL:5	c.-277+39987A>G		intron	N/A	ENSP00000465414.1

Frequencies

GnomAD3 genomes AF: 0.0341 AC: 5177 AN: 152010 Hom.: 300 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0149

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.0318

Gnomad NFE AF: 0.000912

Gnomad OTH AF: 0.0224

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0341 AC: 5189 AN: 152128 Hom.: 301 Cov.: 32 AF XY: 0.0333 AC XY: 2476 AN XY: 74364

African (AFR) AF: 0.116 AC: 4830 AN: 41472

American (AMR) AF: 0.0149 AC: 228 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3470

East Asian (EAS) AF: 0.000773 AC: 4 AN: 5174

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4816

European-Finnish (FIN) AF: 0.0000944 AC: 1 AN: 10596

Middle Eastern (MID) AF: 0.0342 AC: 10 AN: 292

European-Non Finnish (NFE) AF: 0.000912 AC: 62 AN: 67998

Other (OTH) AF: 0.0222 AC: 47 AN: 2116

Alfa AF: 0.0261 Hom.: 24

Bravo AF: 0.0387

Asia WGS AF: 0.00664 AC: 24 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.6
DANN	Benign	0.70
PhyloP100		-0.50
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10421085; hg19: chr19-45622622;