19-42301950-CTC-TTT

Variant names:

• chr19-42301950-CTC-TTT
• NM_002573.4:c.166_168delGAGinsAAA
• PAFAH1B3 p.Glu56Lys

Variant summary

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

The NM_002573.4(PAFAH1B3):​c.166_168delGAGinsAAA​(p.Glu56Lys) variant causes a missense, splice region 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PAFAH1B3 NM_002573.4 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.95
• Publications: 0 publications found

Genes affected

PAFAH1B3 (HGNC:8576): (platelet activating factor acetylhydrolase 1b catalytic subunit 3) This gene encodes an acetylhydrolase that catalyzes the removal of an acetyl group from the glycerol backbone of platelet-activating factor. The encoded enzyme is a subunit of the platelet-activating factor acetylhydrolase isoform 1B complex, which consists of the catalytic beta and gamma subunits and the regulatory alpha subunit. This complex functions in brain development. A translocation between this gene on chromosome 19 and the CDC-like kinase 2 gene on chromosome 1 has been observed, and was associated with cognitive disability, ataxia, and atrophy of the brain. Alternatively spliced transcript variants have been described. [provided by RefSeq, Mar 2009]

PRR19 (HGNC:33728): (proline rich 19)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002573.4. 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
	PAFAH1B3	NM_002573.4	MANE Select	c.166_168delGAGinsAAA	p.Glu56Lys	missense splice_region	N/A	NP_002564.1	Q15102
	PAFAH1B3	NM_001145939.2		c.166_168delGAGinsAAA	p.Glu56Lys	missense splice_region	N/A	NP_001139411.1	A0A024R0L6
	PAFAH1B3	NM_001145940.1		c.166_168delGAGinsAAA	p.Glu56Lys	missense splice_region	N/A	NP_001139412.1	Q15102

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAFAH1B3	ENST00000262890.8	TSL:1 MANE Select	c.166_168delGAGinsAAA	p.Glu56Lys	missense splice_region	N/A	ENSP00000262890.2	Q15102
	PAFAH1B3	ENST00000538771.5	TSL:2	c.166_168delGAGinsAAA	p.Glu56Lys	missense splice_region	N/A	ENSP00000444935.1	Q15102
	PAFAH1B3	ENST00000877854.1		c.166_168delGAGinsAAA	p.Glu56Lys	missense splice_region	N/A	ENSP00000547913.1

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		6.9

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: chr19-42806102;