Variant chr19-7535117-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000601870.1(ENSG00000268614):n.*371+215A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00336 in 282,348 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0055 ( 8 hom., cov: 32)

Exomes 𝑓: 0.00082 ( 2 hom. )

Consequence

ENSG00000268614
ENST00000601870.1 intron

Scores

Splicing: ADA: 0.005729

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0340

Variant links:

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 links:

ENSG00000268614 (HGNC:):

ENSG00000268614 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 19-7535117-A-T is Benign according to our data. Variant chr19-7535117-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 1700443.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00553 (841/152206) while in subpopulation AFR AF= 0.0192 (799/41534). AF 95% confidence interval is 0.0181. There are 8 homozygotes in gnomad4. There are 400 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Protein	UniProt
PNPLA6	NM_001166111.2 linkuse as main transcript	c.-43+215A>T	intron_variant	NP_001159583.1	Q8IY17-4
PNPLA6	NM_001166113.1 linkuse as main transcript	c.-118-10A>T	intron_variant	NP_001159585.1	Q8IY17-2
PNPLA6	NM_006702.5 linkuse as main transcript	c.-43+215A>T	intron_variant	NP_006693.3	Q8IY17-2
PNPLA6	NM_001166112.2 linkuse as main transcript	c.-43+215A>T	intron_variant	NP_001159584.1	Q8IY17-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000268614	ENST00000601870.1 linkuse as main transcript	n.*371+215A>T		intron_variant		4		ENSP00000471492.1		M0R0W3

Frequencies

GnomAD3 genomes

AF:

0.00552

AC:

840

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00335

GnomAD4 exome

AF:

0.000822

AC:

107

AN:

130142

Hom.:

Cov.:

AF XY:

0.000640

AC XY:

AN XY:

68748

show subpopulations

Gnomad4 AFR exome

AF:

0.0184

Gnomad4 AMR exome

AF:

0.000940

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.000880

GnomAD4 genome

AF:

0.00553

AC:

841

AN:

152206

Hom.:

Cov.:

AF XY:

0.00538

AC XY:

400

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0192

Gnomad4 AMR

AF:

0.00190

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00388

Hom.:

Bravo

AF:

0.00625

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 08, 2022

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

8.8

DANN

Benign

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0057

dbscSNV1_RF

Benign

0.026

SpliceAI score (max)

0.14

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over