11-821962-A-T

Variant names:

• chr11-821962-A-T
• NM_020376.4:c.425A>T

Variant summary

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

The NM_020376.4(PNPLA2):​c.425A>T​(p.Asn142Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,690 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PNPLA2 NM_020376.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.07

Genes affected

PNPLA2 (HGNC:30802): (patatin like phospholipase domain containing 2) This gene encodes an enzyme which catalyzes the first step in the hydrolysis of triglycerides in adipose tissue. Mutations in this gene are associated with neutral lipid storage disease with myopathy. [provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNPLA2	NM_020376.4	c.425A>T	p.Asn142Ile	missense_variant	Exon 4 of 10	ENST00000336615.9	NP_065109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNPLA2	ENST00000336615.9	c.425A>T	p.Asn142Ile	missense_variant	Exon 4 of 10	1	NM_020376.4	ENSP00000337701.4
PNPLA2	ENST00000525250.5	n.1031A>T		non_coding_transcript_exon_variant	Exon 2 of 6	2
PNPLA2	ENST00000534561.1	n.92A>T		non_coding_transcript_exon_variant	Exon 2 of 2	2
PNPLA2	ENST00000531923.1	n.-54A>T		upstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461690 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727136

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	0.00089	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	21
DANN	Benign	0.93
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.015
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.088	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	-0.81	N
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	2.0	N
REVEL	Uncertain	0.34
Sift	Benign	0.27	T
Sift4G	Benign	0.31	T
Polyphen		0.63	P
Vest4		0.79
MutPred		0.53		Loss of disorder (P = 0.162);
MVP		0.79
MPC		0.34
ClinPred		0.79	D
GERP RS		4.3
Varity_R		0.14
gMVP		0.66

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-821962;