19-7553027-A-G

Position:

• chr19-7553027-A-G

Variant summary

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

The NM_001166114.2(PNPLA6):​c.2261-848A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.51 (13568 hom., cov: 18)
• Consequence: PNPLA6 NM_001166114.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.147

Genes affected

PNPLA6 (HGNC:16268): (patatin like phospholipase domain containing 6) This gene encodes a phospholipase that deacetylates intracellular phosphatidylcholine to produce glycerophosphocholine. It is thought to function in neurite outgrowth and process elongation during neuronal differentiation. The protein is anchored to the cytoplasmic face of the endoplasmic reticulum in both neurons and non-neuronal cells. Mutations in this gene result in autosomal recessive spastic paraplegia, and the protein is the target for neurodegeneration induced by organophosphorus compounds and chemical warfare agents. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

PNPLA6 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNPLA6	NM_001166114.2	c.2261-848A>G		intron_variant		ENST00000600737.6	NP_001159586.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PNPLA6	ENST00000600737.6	c.2261-848A>G		intron_variant		1	NM_001166114.2	ENSP00000473211.1

Frequencies

GnomAD3 genomes AF: 0.512 AC: 60791 AN: 118824 Hom.: 13556 Cov.: 18

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.630

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.504

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.497

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.512 AC: 60830 AN: 118896 Hom.: 13568 Cov.: 18 AF XY: 0.518 AC XY: 29395 AN XY: 56764

Gnomad4 AFR AF: 0.395

Gnomad4 AMR AF: 0.613

Gnomad4 ASJ AF: 0.481

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.631

Gnomad4 FIN AF: 0.606

Gnomad4 NFE AF: 0.531

Gnomad4 OTH AF: 0.495

Alfa AF: 0.442 Hom.: 7380

Bravo AF: 0.422

Asia WGS AF: 0.432 AC: 1493 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.2
DANN	Benign	0.28

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: rs480208; hg19: chr19-7617913;