rs738408

Variant names:

• chr22-43928850-C-T
• rs738408
• NM_025225.3:c.447C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-43928850-C-T
• chr22-43928850-C-A
• chr22-43928850-C-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_025225.3(PNPLA3):​c.447C>T​(p.Pro149Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 1,606,722 control chromosomes in the GnomAD database, including 47,854 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4553 hom., cov: 30)
  • Exomes 𝑓: 0.23 (43301 hom.)
• Consequence: PNPLA3 NM_025225.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.31
• Publications: 91 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 22-43928850-C-T is Benign according to our data. Variant chr22-43928850-C-T is described in ClinVar as Benign. ClinVar VariationId is 341933.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.31 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.415 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNPLA3	NM_025225.3	MANE Select	c.447C>T	p.Pro149Pro	synonymous	Exon 3 of 9	NP_079501.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNPLA3	ENST00000216180.8	TSL:1 MANE Select	c.447C>T	p.Pro149Pro	synonymous	Exon 3 of 9	ENSP00000216180.3	Q9NST1-1
	PNPLA3	ENST00000862823.1		c.214C>T	p.Leu72Phe	missense	Exon 2 of 6	ENSP00000532882.1
	PNPLA3	ENST00000862822.1		c.477C>T	p.Pro159Pro	synonymous	Exon 3 of 9	ENSP00000532881.1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34587 AN: 151580 Hom.: 4551 Cov.: 30

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.264

GnomAD2 exomes AF: 0.278 AC: 69774 AN: 251164 AF XY: 0.267

Gnomad AFR exome AF: 0.137

Gnomad AMR exome AF: 0.550

Gnomad ASJ exome AF: 0.219

Gnomad EAS exome AF: 0.381

Gnomad FIN exome AF: 0.226

Gnomad NFE exome AF: 0.229

Gnomad OTH exome AF: 0.280

GnomAD4 exome AF: 0.233 AC: 338558 AN: 1455024 Hom.: 43301 Cov.: 35 AF XY: 0.232 AC XY: 167976 AN XY: 724274

African (AFR) AF: 0.132 AC: 4409 AN: 33378

American (AMR) AF: 0.536 AC: 23937 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 5688 AN: 26082

East Asian (EAS) AF: 0.418 AC: 16573 AN: 39648

South Asian (SAS) AF: 0.224 AC: 19261 AN: 86042

European-Finnish (FIN) AF: 0.227 AC: 12110 AN: 53304

Middle Eastern (MID) AF: 0.270 AC: 1552 AN: 5748

European-Non Finnish (NFE) AF: 0.218 AC: 241223 AN: 1106024

Other (OTH) AF: 0.230 AC: 13805 AN: 60124

GnomAD4 genome AF: 0.228 AC: 34593 AN: 151698 Hom.: 4553 Cov.: 30 AF XY: 0.233 AC XY: 17300 AN XY: 74118

African (AFR) AF: 0.139 AC: 5779 AN: 41454

American (AMR) AF: 0.423 AC: 6439 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 733 AN: 3470

East Asian (EAS) AF: 0.386 AC: 1985 AN: 5136

South Asian (SAS) AF: 0.237 AC: 1139 AN: 4800

European-Finnish (FIN) AF: 0.220 AC: 2308 AN: 10494

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.226 AC: 15340 AN: 67828

Other (OTH) AF: 0.261 AC: 549 AN: 2102

Alfa AF: 0.218 Hom.: 1997

Bravo AF: 0.245

Asia WGS AF: 0.296 AC: 1026 AN: 3478

EpiCase AF: 0.238

EpiControl AF: 0.242

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	NAFLD1 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.28
DANN	Benign	0.42
PhyloP100		-2.3
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs738408; hg19: chr22-44324730; COSMIC: COSV53377681; COSMIC: COSV53377681;