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GeneBe

22-43923938-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_025225.3(PNPLA3):c.27C>T(p.Ser9=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000282 in 1,579,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00028 ( 0 hom. )

Consequence

PNPLA3
NM_025225.3 synonymous

Scores

1
1

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.417
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.29).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 22-43923938-C-T is Benign according to our data. Variant chr22-43923938-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2653271.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.417 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PNPLA3NM_025225.3 linkuse as main transcriptc.27C>T p.Ser9= synonymous_variant 1/9 ENST00000216180.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PNPLA3ENST00000216180.8 linkuse as main transcriptc.27C>T p.Ser9= synonymous_variant 1/91 NM_025225.3 P1Q9NST1-1
PNPLA3ENST00000423180.2 linkuse as main transcriptc.27C>T p.Ser9= synonymous_variant 1/92 Q9NST1-2
PNPLA3ENST00000406117.6 linkuse as main transcriptc.27C>T p.Ser9= synonymous_variant, NMD_transcript_variant 1/102

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000328
AC:
50
AN:
152232
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000188
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000632
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000208
AC:
43
AN:
206712
Hom.:
0
AF XY:
0.000208
AC XY:
24
AN XY:
115480
show subpopulations
Gnomad AFR exome
AF:
0.0000943
Gnomad AMR exome
AF:
0.0000313
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000841
Gnomad NFE exome
AF:
0.000419
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000277
AC:
396
AN:
1427682
Hom.:
0
Cov.:
31
AF XY:
0.000301
AC XY:
214
AN XY:
710166
show subpopulations
Gnomad4 AFR exome
AF:
0.0000328
Gnomad4 AMR exome
AF:
0.0000232
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000101
Gnomad4 NFE exome
AF:
0.000343
Gnomad4 OTH exome
AF:
0.000202
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000328
AC:
50
AN:
152232
Hom.:
0
Cov.:
32
AF XY:
0.000296
AC XY:
22
AN XY:
74382
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000188
Gnomad4 NFE
AF:
0.000632
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.000319
Hom.:
0
Bravo
AF:
0.000246

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenSep 01, 2023PNPLA3: PM2:Supporting, BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.29
Cadd
Benign
12
Dann
Uncertain
0.98

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs375838646; hg19: chr22-44319818; API