NM_025225.3:c.79C>A

Variant names:

• chr22-43923990-C-A
• rs756992028
• NM_025225.3:c.79C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025225.3(PNPLA3):​c.79C>A​(p.Arg27Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000419 in 1,432,474 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict 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: 32)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: PNPLA3 NM_025225.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.21

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13216075).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNPLA3	NM_025225.3	c.79C>A	p.Arg27Ser	missense_variant	Exon 1 of 9	ENST00000216180.8	NP_079501.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNPLA3	ENST00000216180.8	c.79C>A	p.Arg27Ser	missense_variant	Exon 1 of 9	1	NM_025225.3	ENSP00000216180.3
PNPLA3	ENST00000423180.2	c.79C>A	p.Arg27Ser	missense_variant	Exon 1 of 9	2		ENSP00000397987.2
PNPLA3	ENST00000406117.6	n.79C>A		non_coding_transcript_exon_variant	Exon 1 of 10	2		ENSP00000384668.2
PNPLA3	ENST00000478713.1	n.-124C>A		upstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000142 AC: 3 AN: 211274 Hom.: 0 AF XY: 0.0000254 AC XY: 3 AN XY: 118006

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000705

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000190

GnomAD4 exome AF: 0.00000419 AC: 6 AN: 1432474 Hom.: 0 Cov.: 31 AF XY: 0.00000561 AC XY: 4 AN XY: 712966

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000475

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000335

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000252 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	6.8
DANN	Benign	0.97
DEOGEN2	Benign	0.051	T;.
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.15	T;T
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	0.78	N;N
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.85	N;N
REVEL	Benign	0.21
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.50	P;.
Vest4		0.14
MutPred		0.63		Loss of methylation at R27 (P = 0.0502);Loss of methylation at R27 (P = 0.0502);
MVP		0.68
MPC		0.23
ClinPred		0.15	T
GERP RS		-0.18
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.13
gMVP		0.26

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: rs756992028; hg19: chr22-44319870;