chr11-74252696-C-T

Variant names:

• chr11-74252696-C-T
• rs500608
• NM_016147.3:c.1143-796C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_016147.3(PPME1):​c.1143-796C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000187 in 341,520 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00016 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00021 (0 hom.)
• Consequence: PPME1 NM_016147.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.38
• Publications: 7 publications found

Genes affected

PPME1 (HGNC:30178): (protein phosphatase methylesterase 1) This gene encodes a protein phosphatase methylesterase localized to the nucleus. The encoded protein acts on the protein phosphatase-2A catalytic subunit and supports the ERK pathway through dephosphorylation of regulatory proteins. It plays a role in malignant glioma progression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2012]

P4HA3 (HGNC:30135): (prolyl 4-hydroxylase subunit alpha 3) This gene encodes a component of prolyl 4-hydroxylase, a key enzyme in collagen synthesis composed of two identical alpha subunits and two beta subunits. The encoded protein is one of several different types of alpha subunits and provides the major part of the catalytic site of the active enzyme. In collagen and related proteins, prolyl 4-hydroxylase catalyzes the formation of 4-hydroxyproline that is essential to the proper three-dimensional folding of newly synthesized procollagen chains. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

ENSG00000206913 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016147.3. 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
	PPME1	NM_016147.3	MANE Select	c.1143-796C>T		intron	N/A	NP_057231.1
	PPME1	NM_001271593.2		c.1185-796C>T		intron	N/A	NP_001258522.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPME1	ENST00000328257.13	TSL:1 MANE Select	c.1143-796C>T		intron	N/A	ENSP00000329867.8
	PPME1	ENST00000398427.6	TSL:1	c.1185-796C>T		intron	N/A	ENSP00000381461.4
	P4HA3	ENST00000524388.5	TSL:1	n.*1319-4695G>A		intron	N/A	ENSP00000433860.1

Frequencies

GnomAD3 genomes AF: 0.000164 AC: 25 AN: 152014 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.000479

GnomAD4 exome AF: 0.000206 AC: 39 AN: 189388 Hom.: 0 AF XY: 0.000183 AC XY: 19 AN XY: 103812

African (AFR) AF: 0.00 AC: 0 AN: 5368

American (AMR) AF: 0.000702 AC: 9 AN: 12824

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4310

East Asian (EAS) AF: 0.00 AC: 0 AN: 8092

South Asian (SAS) AF: 0.00 AC: 0 AN: 39452

European-Finnish (FIN) AF: 0.000125 AC: 1 AN: 7986

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 640

European-Non Finnish (NFE) AF: 0.000275 AC: 28 AN: 101658

Other (OTH) AF: 0.000110 AC: 1 AN: 9058

GnomAD4 genome AF: 0.000164 AC: 25 AN: 152132 Hom.: 0 Cov.: 31 AF XY: 0.000108 AC XY: 8 AN XY: 74380

African (AFR) AF: 0.0000482 AC: 2 AN: 41516

American (AMR) AF: 0.000131 AC: 2 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 67988

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.00 Hom.: 21906

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.062
DANN	Benign	0.48
PhyloP100		-2.4

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: rs500608; hg19: chr11-73963741;