rs3812499

Variant names:

• chr9-137478118-G-A
• rs3812499
• NM_001098537.3:c.2798C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098537.3. 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
	PNPLA7	NM_001098537.3	MANE Select	c.2798C>T	p.Pro933Leu	missense	Exon 25 of 35	NP_001092007.2	Q6ZV29-5
	PNPLA7	NM_152286.5		c.2723C>T	p.Pro908Leu	missense	Exon 24 of 34	NP_689499.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNPLA7	ENST00000406427.6	TSL:1 MANE Select	c.2798C>T	p.Pro933Leu	missense	Exon 25 of 35	ENSP00000384610.1	Q6ZV29-5
	PNPLA7	ENST00000946238.1		c.2915C>T	p.Pro972Leu	missense	Exon 25 of 35	ENSP00000616297.1
	PNPLA7	ENST00000882824.1		c.2882C>T	p.Pro961Leu	missense	Exon 25 of 35	ENSP00000552883.1

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

GnomAD2 exomes AF: 0.00739 AC: 253 AN: 34230 AF XY: 0.00742

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 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

African (AFR) AF: 0.000797 AC: 19 AN: 23850

American (AMR) AF: 0.000283 AC: 3 AN: 10608

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16662

East Asian (EAS) AF: 0.144 AC: 3942 AN: 27306

South Asian (SAS) AF: 0.00259 AC: 121 AN: 46660

European-Finnish (FIN) AF: 0.00186 AC: 80 AN: 42896

Middle Eastern (MID) AF: 0.00143 AC: 7 AN: 4888

European-Non Finnish (NFE) AF: 0.000520 AC: 507 AN: 974322

Other (OTH) AF: 0.00773 AC: 372 AN: 48154

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

African (AFR) AF: 0.00171 AC: 71 AN: 41566

American (AMR) AF: 0.000719 AC: 11 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.120 AC: 621 AN: 5174

South Asian (SAS) AF: 0.00767 AC: 37 AN: 4824

European-Finnish (FIN) AF: 0.00169 AC: 18 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000603 AC: 41 AN: 67988

Other (OTH) AF: 0.00473 AC: 10 AN: 2112

Alfa AF: 0.00438 Hom.: 46

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 v4.9

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
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		9.3
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.013	D
Polyphen		0.89	P
Vest4		0.46
MVP		0.19
MPC		0.62
ClinPred		0.099	T
GERP RS		4.7
Varity_R		0.22
gMVP		0.52
Mutation Taster		=81/19	polymorphism (auto)

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

Other links and lift over

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