NM_025225.3:c.1112+305A>G

Variant names:

• chr22-43940430-A-G
• rs1010022
• NM_025225.3:c.1112+305A>G

Variant summary

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

The NM_025225.3(PNPLA3):​c.1112+305A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,176 control chromosomes in the GnomAD database, including 3,660 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 0.20 (3660 hom., cov: 32)
• Consequence: PNPLA3 NM_025225.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.425
• Publications: 6 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025225.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNPLA3	NM_025225.3	MANE Select	c.1112+305A>G		intron	N/A	NP_079501.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNPLA3	ENST00000216180.8	TSL:1 MANE Select	c.1112+305A>G		intron	N/A	ENSP00000216180.3
	PNPLA3	ENST00000423180.2	TSL:2	c.1100+305A>G		intron	N/A	ENSP00000397987.2
	PNPLA3	ENST00000406117.6	TSL:2	n.*744+305A>G		intron	N/A	ENSP00000384668.2

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30921 AN: 152058 Hom.: 3660 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.208

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.203 AC: 30928 AN: 152176 Hom.: 3660 Cov.: 32 AF XY: 0.211 AC XY: 15700 AN XY: 74408

African (AFR) AF: 0.166 AC: 6880 AN: 41524

American (AMR) AF: 0.375 AC: 5725 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 553 AN: 3464

East Asian (EAS) AF: 0.393 AC: 2029 AN: 5164

South Asian (SAS) AF: 0.224 AC: 1076 AN: 4814

European-Finnish (FIN) AF: 0.230 AC: 2439 AN: 10592

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11570 AN: 68014

Other (OTH) AF: 0.207 AC: 437 AN: 2116

Alfa AF: 0.183 Hom.: 413

Bravo AF: 0.217

Asia WGS AF: 0.291 AC: 1010 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.67
PhyloP100		-0.42
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1010022; hg19: chr22-44336310;