1-202463032-T-G

Variant names:

• chr1-202463032-T-G
• rs3767421
• ENST00000290419.9:c.-538T>G

Variant summary

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

The ENST00000290419.9(PPP1R12B):​c.-538T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 984,590 control chromosomes in the GnomAD database, including 113,748 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 0.43 (15686 hom., cov: 32)
  • Exomes 𝑓: 0.48 (98062 hom.)
• Consequence: PPP1R12B ENST00000290419.9 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.716
• Publications: 4 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R12B	NM_002481.4	c.1850+13861T>G		intron_variant	Intron 13 of 23	ENST00000608999.6	NP_002472.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R12B	ENST00000608999.6	c.1850+13861T>G		intron_variant	Intron 13 of 23	1	NM_002481.4	ENSP00000476755.1

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65967 AN: 151980 Hom.: 15677 Cov.: 32

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.630

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.423

GnomAD4 exome AF: 0.483 AC: 402016 AN: 832492 Hom.: 98062 Cov.: 31 AF XY: 0.484 AC XY: 185908 AN XY: 384464

African (AFR) AF: 0.219 AC: 3458 AN: 15778

American (AMR) AF: 0.632 AC: 621 AN: 982

Ashkenazi Jewish (ASJ) AF: 0.377 AC: 1943 AN: 5148

East Asian (EAS) AF: 0.693 AC: 2517 AN: 3630

South Asian (SAS) AF: 0.603 AC: 9911 AN: 16448

European-Finnish (FIN) AF: 0.449 AC: 124 AN: 276

Middle Eastern (MID) AF: 0.398 AC: 645 AN: 1620

European-Non Finnish (NFE) AF: 0.485 AC: 369352 AN: 761336

Other (OTH) AF: 0.493 AC: 13445 AN: 27274

GnomAD4 genome AF: 0.434 AC: 65990 AN: 152098 Hom.: 15686 Cov.: 32 AF XY: 0.438 AC XY: 32584 AN XY: 74342

African (AFR) AF: 0.253 AC: 10494 AN: 41520

American (AMR) AF: 0.578 AC: 8831 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1270 AN: 3468

East Asian (EAS) AF: 0.706 AC: 3652 AN: 5170

South Asian (SAS) AF: 0.629 AC: 3030 AN: 4820

European-Finnish (FIN) AF: 0.462 AC: 4876 AN: 10564

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.478 AC: 32477 AN: 67950

Other (OTH) AF: 0.426 AC: 900 AN: 2112

Alfa AF: 0.394 Hom.: 2841

Bravo AF: 0.433

Asia WGS AF: 0.630 AC: 2189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.67
PhyloP100		-0.72
PromoterAI		0.036	Neutral
Mutation Taster		=300/0	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: rs3767421; hg19: chr1-202432160; COSMIC: COSV51782977;