ENST00000423180:c.-108T>C

Variant names:

• chr22-43923804-T-C
• rs2049901492
• ENST00000862819.1:c.-108T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000423180.2(PNPLA3):​c.-108T>C variant causes a 5 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PNPLA3 ENST00000423180.2 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.854
• Publications: 0 publications found

Genes affected

PNPLA3 (HGNC:18590): (patatin like phospholipase domain containing 3) The protein encoded by this gene is a triacylglycerol lipase that mediates triacylglycerol hydrolysis in adipocytes. The encoded protein, which appears to be membrane bound, may be involved in the balance of energy usage/storage in adipocytes. [provided by RefSeq, Jul 2008]

ENSG00000304926 (HGNC:):

ACMG classification

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=-0.87).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000423180.2. 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
	PNPLA3	NM_025225.3	MANE Select	c.-108T>C		upstream_gene	N/A	NP_079501.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNPLA3	ENST00000862819.1		c.-108T>C		5_prime_UTR	Exon 1 of 9	ENSP00000532878.1
	PNPLA3	ENST00000862820.1		c.-108T>C		5_prime_UTR	Exon 1 of 9	ENSP00000532879.1
	PNPLA3	ENST00000423180.2	TSL:2	c.-108T>C		5_prime_UTR	Exon 1 of 9	ENSP00000397987.2	Q9NST1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 964256 Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0 AN XY: 475702

African (AFR) AF: 0.00 AC: 0 AN: 18762

American (AMR) AF: 0.00 AC: 0 AN: 13338

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15864

East Asian (EAS) AF: 0.00 AC: 0 AN: 26646

South Asian (SAS) AF: 0.00 AC: 0 AN: 50664

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3142

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 764112

Other (OTH) AF: 0.00 AC: 0 AN: 42314

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	NAFLD1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.3
DANN	Benign	0.60
PhyloP100		0.85
PromoterAI		0.032	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs2049901492; hg19: chr22-44319684;