rs3812499

Positions:

• chr9-137478118-G-A
• chr9-137478118-G-C
• chr9-137478118-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098537.3(PNPLA7):​c.2798C>T​(p.Pro933Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00435 in 1,347,618 control chromosomes in the GnomAD database, including 370 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 0.0053 (51 hom., cov: 33)
  • Exomes 𝑓: 0.0042 (319 hom.)
• Consequence: PNPLA7 NM_001098537.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.26

Genes affected

PNPLA7 (HGNC:24768): (patatin like phospholipase domain containing 7) Human patatin-like phospholipases, such as PNPLA7, have been implicated in regulation of adipocyte differentiation and have been induced by metabolic stimuli (Wilson et al., 2006 [PubMed 16799181]).[supplied by OMIM, Jun 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019916296).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PNPLA7	NM_001098537.3	c.2798C>T	p.Pro933Leu	missense_variant	25/35	ENST00000406427.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PNPLA7	ENST00000406427.6	c.2798C>T	p.Pro933Leu	missense_variant	25/35	1	NM_001098537.3	P2
PNPLA7	ENST00000277531.8	c.2723C>T	p.Pro908Leu	missense_variant	24/34	2		A2
PNPLA7	ENST00000469998.1	n.1537C>T		non_coding_transcript_exon_variant	2/10	2
PNPLA7	ENST00000492278.5	n.1314C>T		non_coding_transcript_exon_variant	1/5	2

Frequencies

GnomAD3 genomes AF: 0.00533 AC: 811 AN: 152154 Hom.: 52 Cov.: 33

Gnomad AFR AF: 0.00171

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.00766

Gnomad FIN AF: 0.00169

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000603

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00739 AC: 253 AN: 34230 Hom.: 17 AF XY: 0.00742 AC XY: 117 AN XY: 15770

Gnomad AFR exome AF: 0.00141

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.150

Gnomad SAS exome AF: 0.00622

Gnomad FIN exome AF: 0.00214

Gnomad NFE exome AF: 0.000518

Gnomad OTH exome AF: 0.00871

GnomAD4 exome AF: 0.00423 AC: 5051 AN: 1195346 Hom.: 319 Cov.: 30 AF XY: 0.00409 AC XY: 2357 AN XY: 576490

Gnomad4 AFR exome AF: 0.000797

Gnomad4 AMR exome AF: 0.000283

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.144

Gnomad4 SAS exome AF: 0.00259

Gnomad4 FIN exome AF: 0.00186

Gnomad4 NFE exome AF: 0.000520

Gnomad4 OTH exome AF: 0.00773

GnomAD4 genome AF: 0.00532 AC: 810 AN: 152272 Hom.: 51 Cov.: 33 AF XY: 0.00625 AC XY: 465 AN XY: 74446

Gnomad4 AFR AF: 0.00171

Gnomad4 AMR AF: 0.000719

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.00767

Gnomad4 FIN AF: 0.00169

Gnomad4 NFE AF: 0.000603

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00379 Hom.: 23

Bravo AF: 0.00564

ESP6500AA AF: 0.00163 AC: 7

ESP6500EA AF: 0.000354 AC: 3

ExAC AF: 0.00598 AC: 631

Asia WGS AF: 0.0520 AC: 180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.074	T;.
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D;D
MetaRNN	Benign	0.0020	T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.5	M;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-5.7	D;D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.013	D;D
Polyphen		0.89	P;D
Vest4		0.46
MVP		0.19
MPC		0.62
ClinPred		0.099	T
GERP RS		4.7
Varity_R		0.22
gMVP		0.52

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: rs3812499; hg19: chr9-140372570; COSMIC: COSV53006481;