Genetic Variant PMAIP1:c.*348G>A (chr18-59903101-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_021127.3(PMAIP1):c.*348G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,160 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 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PMAIP1
NM_021127.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.413

Publications

10 publications found

Variant links:

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]

PMAIP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PMAIP1	NM_021127.3	MANE Select	c.*348G>A	3_prime_UTR	Exon 2 of 2	NP_066950.1
PMAIP1	NM_001382616.1		c.*253G>A	3_prime_UTR	Exon 3 of 3	NP_001369545.1
PMAIP1	NM_001382618.1		c.*253G>A	3_prime_UTR	Exon 3 of 3	NP_001369547.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PMAIP1	ENST00000316660.7	TSL:1 MANE Select	c.*348G>A	3_prime_UTR	Exon 2 of 2	ENSP00000326119.7
PMAIP1	ENST00000269518.9	TSL:1	c.*253G>A	3_prime_UTR	Exon 3 of 3	ENSP00000269518.9
PMAIP1	ENST00000590596.1	TSL:3	n.*138G>A	downstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

389194

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

204762

African (AFR)

AF:

0.00

AC:

AN:

11428

American (AMR)

AF:

0.00

AC:

AN:

15350

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12386

East Asian (EAS)

AF:

0.00

AC:

AN:

26572

South Asian (SAS)

AF:

0.00

AC:

AN:

40922

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23204

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1716

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

234908

Other (OTH)

AF:

0.00

AC:

AN:

22708

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41450

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

1102

Bravo

AF:

0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.3

(source)

DANN

Benign

0.63

PhyloP100

0.41

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over