6-36291158-T-G

Position:

• chr6-36291158-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001374623.1(PNPLA1):​c.206-162T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 152,202 control chromosomes in the GnomAD database, including 5,080 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.23 (5080 hom., cov: 31)
• Consequence: PNPLA1 NM_001374623.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.338

Genes affected

PNPLA1 (HGNC:21246): (patatin like phospholipase domain containing 1) The protein encoded by this gene belongs to the patatin-like phospholipase (PNPLA) family, which is characterized by the presence of a highly conserved patatin domain. PNPLA family members have diverse lipolytic and acyltransferase activities, and are key elements in lipid metabolism. While other members of this family have been well characterized, the function of this gene remained an enigma. However, recent studies show that this gene is expressed in the skin epidermal keratinocytes, and has a role in glycerophospholipid metabolism in the cutaneous barrier. Consistent with these observations, mutations in this gene are associated with ichthyosis in human (autosomal recessive congenital ichthyoses, ARCI) and dog. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2012]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 6-36291158-T-G is Benign according to our data. Variant chr6-36291158-T-G is described in ClinVar as [Benign]. Clinvar id is 1282783.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PNPLA1	NM_001374623.1	c.206-162T>G		intron_variant		ENST00000636260.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PNPLA1	ENST00000636260.2	c.206-162T>G		intron_variant		5	NM_001374623.1	A2

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35184 AN: 152084 Hom.: 5076 Cov.: 31

Gnomad AFR AF: 0.0626

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.231 AC: 35182 AN: 152202 Hom.: 5080 Cov.: 31 AF XY: 0.233 AC XY: 17348 AN XY: 74398

Gnomad4 AFR AF: 0.0624

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.223

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.245

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.322

Gnomad4 OTH AF: 0.184

Alfa AF: 0.291 Hom.: 6869

Bravo AF: 0.209

Asia WGS AF: 0.165 AC: 574 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.3
DANN	Benign	0.50

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: rs9394342; hg19: chr6-36258935; COSMIC: COSV57232359; COSMIC: COSV57232359;