rs2029721

Positions:

• chr12-62755564-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020700.2(PPM1H):​c.870-17978C>T variant causes a intron change. The variant allele was found at a frequency of 0.332 in 653,130 control chromosomes in the GnomAD database, including 38,593 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 0.29 (7471 hom., cov: 31)
  • Exomes 𝑓: 0.34 (31122 hom.)
• Consequence: PPM1H NM_020700.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.97

Genes affected

PPM1H (HGNC:18583): (protein phosphatase, Mg2+/Mn2+ dependent 1H) Enables identical protein binding activity and phosphoprotein phosphatase activity. Predicted to be involved in protein dephosphorylation. Located in cytoplasm and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

GAPDHP44 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPM1H	NM_020700.2	c.870-17978C>T		intron_variant		ENST00000228705.7	NP_065751.1
PPM1H	XM_011538578.3	c.756-17978C>T		intron_variant			XP_011536880.1
PPM1H	XM_017019676.3	c.870-17978C>T		intron_variant			XP_016875165.1
GAPDHP44		n.62755564G>A		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPM1H	ENST00000228705.7	c.870-17978C>T		intron_variant		1	NM_020700.2	ENSP00000228705.5
GAPDHP44	ENST00000513513.1	n.338G>A		non_coding_transcript_exon_variant	1/1	6
PPM1H	ENST00000551519.1	n.260-17978C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43880 AN: 151888 Hom.: 7471 Cov.: 31

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.305

GnomAD4 exome AF: 0.345 AC: 172767 AN: 501124 Hom.: 31122 Cov.: 2 AF XY: 0.341 AC XY: 92932 AN XY: 272180

Gnomad4 AFR exome AF: 0.112

Gnomad4 AMR exome AF: 0.377

Gnomad4 ASJ exome AF: 0.275

Gnomad4 EAS exome AF: 0.219

Gnomad4 SAS exome AF: 0.280

Gnomad4 FIN exome AF: 0.424

Gnomad4 NFE exome AF: 0.376

Gnomad4 OTH exome AF: 0.335

GnomAD4 genome AF: 0.289 AC: 43881 AN: 152006 Hom.: 7471 Cov.: 31 AF XY: 0.289 AC XY: 21506 AN XY: 74304

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.326

Gnomad4 ASJ AF: 0.288

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.284

Gnomad4 FIN AF: 0.433

Gnomad4 NFE AF: 0.370

Gnomad4 OTH AF: 0.302

Alfa AF: 0.342 Hom.: 1242

Bravo AF: 0.275

Asia WGS AF: 0.240 AC: 839 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	5.1
DANN	Benign	0.78

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: rs2029721; hg19: chr12-63149344;