18-59903101-G-T

Variant names:

• chr18-59903101-G-T
• rs1041978
• NM_021127.3:c.*348G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021127.3(PMAIP1):​c.*348G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 541,012 control chromosomes in the GnomAD database, including 3,923 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 0.094 (821 hom., cov: 33)
  • Exomes 𝑓: 0.12 (3102 hom.)
• Consequence: PMAIP1 NM_021127.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.413
• Publications: 10 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

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.*348G>T		3_prime_UTR	Exon 2 of 2	NP_066950.1	A0A0S2Z490
	PMAIP1	NM_001382616.1		c.*253G>T		3_prime_UTR	Exon 3 of 3	NP_001369545.1	Q13794-2
	PMAIP1	NM_001382618.1		c.*253G>T		3_prime_UTR	Exon 3 of 3	NP_001369547.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PMAIP1	ENST00000316660.7	TSL:1 MANE Select	c.*348G>T		3_prime_UTR	Exon 2 of 2	ENSP00000326119.7	Q13794-1
	PMAIP1	ENST00000269518.9	TSL:1	c.*253G>T		3_prime_UTR	Exon 3 of 3	ENSP00000269518.9	Q13794-2
	PMAIP1	ENST00000919087.1		c.*348G>T		downstream_gene	N/A	ENSP00000589146.1

Frequencies

GnomAD3 genomes AF: 0.0946 AC: 14386 AN: 152140 Hom.: 821 Cov.: 33

Gnomad AFR AF: 0.0360

Gnomad AMI AF: 0.0231

Gnomad AMR AF: 0.0892

Gnomad ASJ AF: 0.0908

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.0946

GnomAD4 exome AF: 0.120 AC: 46593 AN: 388754 Hom.: 3102 Cov.: 2 AF XY: 0.121 AC XY: 24651 AN XY: 204502

African (AFR) AF: 0.0353 AC: 403 AN: 11426

American (AMR) AF: 0.102 AC: 1560 AN: 15334

Ashkenazi Jewish (ASJ) AF: 0.0938 AC: 1161 AN: 12374

East Asian (EAS) AF: 0.217 AC: 5749 AN: 26536

South Asian (SAS) AF: 0.119 AC: 4861 AN: 40882

European-Finnish (FIN) AF: 0.119 AC: 2750 AN: 23174

Middle Eastern (MID) AF: 0.0998 AC: 171 AN: 1714

European-Non Finnish (NFE) AF: 0.117 AC: 27477 AN: 234626

Other (OTH) AF: 0.108 AC: 2461 AN: 22688

GnomAD4 genome AF: 0.0944 AC: 14377 AN: 152258 Hom.: 821 Cov.: 33 AF XY: 0.0947 AC XY: 7047 AN XY: 74430

African (AFR) AF: 0.0360 AC: 1495 AN: 41570

American (AMR) AF: 0.0891 AC: 1363 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0908 AC: 315 AN: 3470

East Asian (EAS) AF: 0.226 AC: 1168 AN: 5168

South Asian (SAS) AF: 0.116 AC: 561 AN: 4826

European-Finnish (FIN) AF: 0.112 AC: 1189 AN: 10590

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.118 AC: 8039 AN: 68010

Other (OTH) AF: 0.0936 AC: 198 AN: 2116

Alfa AF: 0.0989 Hom.: 1102

Bravo AF: 0.0917

Asia WGS AF: 0.141 AC: 492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.7
DANN	Benign	0.62
PhyloP100		0.41
Mutation Taster		=100/0	polymorphism (auto)

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: rs1041978; hg19: chr18-57570333;