9-137478118-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001098537.3(PNPLA7):​c.2798C>A​(p.Pro933Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000167 in 1,195,354 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000017 (0 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.777

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNPLA7	NM_001098537.3	MANE Select	c.2798C>A	p.Pro933Gln	missense	Exon 25 of 35	NP_001092007.2
	PNPLA7	NM_152286.5		c.2723C>A	p.Pro908Gln	missense	Exon 24 of 34	NP_689499.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNPLA7	ENST00000406427.6	TSL:1 MANE Select	c.2798C>A	p.Pro933Gln	missense	Exon 25 of 35	ENSP00000384610.1
	PNPLA7	ENST00000277531.8	TSL:2	c.2723C>A	p.Pro908Gln	missense	Exon 24 of 34	ENSP00000277531.4
	PNPLA7	ENST00000469998.1	TSL:2	n.1537C>A		non_coding_transcript_exon	Exon 2 of 10

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000167 AC: 2 AN: 1195354 Hom.: 0 Cov.: 30 AF XY: 0.00000173 AC XY: 1 AN XY: 576496

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 23850

American (AMR) AF: 0.00 AC: 0 AN: 10608

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 27310

South Asian (SAS) AF: 0.00 AC: 0 AN: 46662

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42896

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4888

European-Non Finnish (NFE) AF: 0.00000205 AC: 2 AN: 974324

Other (OTH) AF: 0.00 AC: 0 AN: 48154

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 46

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	0.0034	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.063	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.045	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.9	L
PhyloP100		9.3
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.26
Sift	Benign	0.040	D
Sift4G	Benign	0.086	T
Polyphen		0.98	D
Vest4		0.52
MutPred		0.20		Loss of catalytic residue at P907 (P = 0.0185)
MVP		0.27
MPC		0.67
ClinPred		1.0	D
GERP RS		4.7
Varity_R		0.19
gMVP		0.49
Mutation Taster		=59/41	polymorphism

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;