18-59902724-ATA-CTC

Variant names:

• chr18-59902724-ATA-CTC
• NM_021127.3:c.136_138delATAinsCTC
• PMAIP1 p.Ile46Leu

Variant summary

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

The NM_021127.3(PMAIP1):​c.136_138delATAinsCTC​(p.Ile46Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 33)
• Consequence: PMAIP1 NM_021127.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.56
• Publications: 0 publications found

Genes affected

PMAIP1 (HGNC:9108): (phorbol-12-myristate-13-acetate-induced protein 1) This gene belongs to a pro-apoptotic subfamily within the BCL-2 protein family, referred to as the BCL-2 homology domain 3 (BH3)-only subfamily, which determine whether a cell commits to apoptosis. In response to death-inducing stimuli, BH3-only members inhibit the anti-apoptotic BCL-2 family members, which under steady-state conditions keep the multi-BH domain proteins BAX and BAK, in an inactive state. [provided by RefSeq, Aug 2020]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021127.3. 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
	PMAIP1	NM_021127.3	MANE Select	c.136_138delATAinsCTC	p.Ile46Leu	missense	N/A	NP_066950.1	A0A0S2Z490
	PMAIP1	NM_001382616.1		c.287_289delATAinsCTC	p.AspIle96AlaLeu	missense	N/A	NP_001369545.1	Q13794-2
	PMAIP1	NM_001382618.1		c.281_283delATAinsCTC	p.AspIle94AlaLeu	missense	N/A	NP_001369547.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PMAIP1	ENST00000316660.7	TSL:1 MANE Select	c.136_138delATAinsCTC	p.Ile46Leu	missense	N/A	ENSP00000326119.7	Q13794-1
	PMAIP1	ENST00000269518.9	TSL:1	c.287_289delATAinsCTC	p.AspIle96AlaLeu	missense	N/A	ENSP00000269518.9	Q13794-2
	PMAIP1	ENST00000919087.1		c.136_138delATAinsCTC	p.Ile46Leu	missense	N/A	ENSP00000589146.1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.6

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: chr18-57569956;