19-7534329-C-T

Position:

• chr19-7534329-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000601870.1(ENSG00000268614):​n.*151-50C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 216,762 control chromosomes in the GnomAD database, including 6,898 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5009 hom., cov: 31)
  • Exomes 𝑓: 0.22 (1889 hom.)
• Consequence: ENSG00000268614 ENST00000601870.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.306

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]

ENSG00000268614 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 19-7534329-C-T is Benign according to our data. Variant chr19-7534329-C-T is described in ClinVar as [Benign]. Clinvar id is 1526319.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNPLA6	NM_001166112.2	c.-313C>T		5_prime_UTR_premature_start_codon_gain_variant	1/34		NP_001159584.1
PNPLA6	NM_001166112.2	c.-313C>T		5_prime_UTR_variant	1/34		NP_001159584.1
PNPLA6	NM_006702.5	c.-196+90C>T		intron_variant			NP_006693.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000268614	ENST00000601870.1	n.*151-50C>T		intron_variant		4		ENSP00000471492.1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38344 AN: 151824 Hom.: 4988 Cov.: 31

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.220

GnomAD4 exome AF: 0.221 AC: 14296 AN: 64818 Hom.: 1889 Cov.: 0 AF XY: 0.215 AC XY: 7379 AN XY: 34368

Gnomad4 AFR exome AF: 0.168

Gnomad4 AMR exome AF: 0.293

Gnomad4 ASJ exome AF: 0.0953

Gnomad4 EAS exome AF: 0.282

Gnomad4 SAS exome AF: 0.190

Gnomad4 FIN exome AF: 0.236

Gnomad4 NFE exome AF: 0.224

Gnomad4 OTH exome AF: 0.219

GnomAD4 genome AF: 0.253 AC: 38396 AN: 151944 Hom.: 5009 Cov.: 31 AF XY: 0.251 AC XY: 18656 AN XY: 74258

Gnomad4 AFR AF: 0.214

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.146

Gnomad4 EAS AF: 0.295

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.307

Gnomad4 NFE AF: 0.267

Gnomad4 OTH AF: 0.221

Alfa AF: 0.267 Hom.: 1131

Bravo AF: 0.250

Asia WGS AF: 0.288 AC: 998 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 28, 2022	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.7
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs540516; hg19: chr19-7599215;