chr22-43880291-T-G

Position:

• chr22-43880291-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000216177.9(PNPLA5):​c.*504A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.872 in 397,602 control chromosomes in the GnomAD database, including 151,886 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 0.88 (59865 hom., cov: 34)
  • Exomes 𝑓: 0.86 (92021 hom.)
• Consequence: PNPLA5 ENST00000216177.9 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330

Genes affected

PNPLA5 (HGNC:24888): (patatin like phospholipase domain containing 5) This gene is a member of the patatin-like phospholipase family; its encoded protein has been shown to inhibit transacylation. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Apr 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNPLA5	NM_138814.4	c.*504A>C		3_prime_UTR_variant	9/9	ENST00000216177.9	NP_620169.1
PNPLA5	NM_001177675.2	c.*504A>C		3_prime_UTR_variant	7/7		NP_001171146.1
PNPLA5	NM_001371410.1	c.*504A>C		3_prime_UTR_variant	9/9		NP_001358339.1
PNPLA5	XM_047441164.1	c.*504A>C		3_prime_UTR_variant	7/7		XP_047297120.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PNPLA5	ENST00000216177.9	c.*504A>C		3_prime_UTR_variant	9/9	1	NM_138814.4	ENSP00000216177	P1
PNPLA5	ENST00000381198.7	c.*504A>C		3_prime_UTR_variant	7/7	2		ENSP00000370595

Frequencies

GnomAD3 genomes AF: 0.885 AC: 134597 AN: 152150 Hom.: 59803 Cov.: 34

Gnomad AFR AF: 0.943

Gnomad AMI AF: 0.936

Gnomad AMR AF: 0.877

Gnomad ASJ AF: 0.773

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.946

Gnomad FIN AF: 0.921

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.838

Gnomad OTH AF: 0.860

GnomAD4 exome AF: 0.864 AC: 212006 AN: 245334 Hom.: 92021 Cov.: 0 AF XY: 0.862 AC XY: 107249 AN XY: 124396

Gnomad4 AFR exome AF: 0.945

Gnomad4 AMR exome AF: 0.888

Gnomad4 ASJ exome AF: 0.778

Gnomad4 EAS exome AF: 0.992

Gnomad4 SAS exome AF: 0.951

Gnomad4 FIN exome AF: 0.907

Gnomad4 NFE exome AF: 0.839

Gnomad4 OTH exome AF: 0.864

GnomAD4 genome AF: 0.885 AC: 134720 AN: 152268 Hom.: 59865 Cov.: 34 AF XY: 0.889 AC XY: 66154 AN XY: 74440

Gnomad4 AFR AF: 0.943

Gnomad4 AMR AF: 0.877

Gnomad4 ASJ AF: 0.773

Gnomad4 EAS AF: 0.994

Gnomad4 SAS AF: 0.946

Gnomad4 FIN AF: 0.921

Gnomad4 NFE AF: 0.838

Gnomad4 OTH AF: 0.861

Alfa AF: 0.842 Hom.: 64838

Bravo AF: 0.883

Asia WGS AF: 0.966 AC: 3360 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.5
DANN	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs470093; hg19: chr22-44276171;