1-202558893-GG-AA

Variant names:

• chr1-202558893-GG-AA
• NM_002481.4:c.2507_2507+1delGGinsAA
• PPP1R12B p.Arg836Lys

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PVS1_Moderate

The NM_002481.4(PPP1R12B):​c.2507_2507+1delGGinsAA​(p.Arg836Lys) variant causes a splice donor, missense, intron change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPP1R12B NM_002481.4 splice_donor, missense, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.82
• Publications: 0 publications found

Genes affected

PPP1R12B (HGNC:7619): (protein phosphatase 1 regulatory subunit 12B) Myosin phosphatase is a protein complex comprised of three subunits: a catalytic subunit (PP1c-delta, protein phosphatase 1, catalytic subunit delta), a large regulatory subunit (MYPT, myosin phosphatase target) and small regulatory subunit (sm-M20). Two isoforms of MYPT have been isolated--MYPT1 and MYPT2, the first of which is widely expressed, and the second of which may be specific to heart, skeletal muscle, and brain. Each of the MYPT isoforms functions to bind PP1c-delta and increase phosphatase activity. This locus encodes both MYTP2 and M20. Alternatively spliced transcript variants encoding different isoforms have been identified. Related pseudogenes have been defined on the Y chromosome. [provided by RefSeq, Oct 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.005764666 fraction of the gene. Cryptic splice site detected, with MaxEntScore 7.2, offset of 39, new splice context is: cttGTgagt. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002481.4. 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
	PPP1R12B	NM_002481.4	MANE Select	c.2507_2507+1delGGinsAA	p.Arg836Lys	splice_donor missense intron	N/A	NP_002472.2	O60237-1
	PPP1R12B	NM_001331029.2		c.2690_2690+1delGGinsAA	p.Arg897Lys	splice_donor missense intron	N/A	NP_001317958.1	O60237-6
	PPP1R12B	NM_001410283.1		c.2507_2507+1delGGinsAA	p.Arg836Lys	splice_donor missense intron	N/A	NP_001397212.1	A0A994J7P4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R12B	ENST00000608999.6	TSL:1 MANE Select	c.2507_2507+1delGGinsAA	p.Arg836Lys	splice_donor missense intron	N/A	ENSP00000476755.1	O60237-1
	PPP1R12B	ENST00000290419.9	TSL:1	c.185_185+1delGGinsAA	p.Arg62Lys	splice_donor missense splice_region intron	N/A	ENSP00000484005.1	O60237-3
	PPP1R12B	ENST00000491336.5	TSL:1	c.185_185+1delGGinsAA	p.Arg62Lys	splice_donor missense splice_region intron	N/A	ENSP00000480852.1	O60237-4

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.8

Splicing

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

hg19: chr1-202528021;