22-43880291-T-C

Position:

• chr22-43880291-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_138814.4(PNPLA5):​c.*504A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 34)
• Consequence: PNPLA5 NM_138814.4 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.4
DANN	Benign	0.84

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

LitVar

Other links and lift over

dbSNP: rs470093; hg19: chr22-44276171;