3-171603524-T-C

Position:

• chr3-171603524-T-C

Variant summary

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

The NM_002662.5(PLD1):​c.3001-222A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 151,974 control chromosomes in the GnomAD database, including 20,568 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.51 (20568 hom., cov: 32)
• Consequence: PLD1 NM_002662.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.33

Genes affected

PLD1 (HGNC:9067): (phospholipase D1) This gene encodes a phosphatidylcholine-specific phospholipase which catalyzes the hydrolysis of phosphatidylcholine in order to yield phosphatidic acid and choline. The enzyme may play a role in signal transduction and subcellular trafficking. Alternative splicing results in multiple transcript variants with both catalytic and regulatory properties. [provided by RefSeq, Sep 2011]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 3-171603524-T-C is Benign according to our data. Variant chr3-171603524-T-C is described in ClinVar as [Benign]. Clinvar id is 1224136.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLD1	NM_002662.5	c.3001-222A>G		intron_variant		ENST00000351298.9	NP_002653.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLD1	ENST00000351298.9	c.3001-222A>G		intron_variant		1	NM_002662.5	ENSP00000342793	A1
PLD1	ENST00000356327.9	c.2887-222A>G		intron_variant		1		ENSP00000348681	P4

Frequencies

GnomAD3 genomes AF: 0.507 AC: 77035 AN: 151856 Hom.: 20519 Cov.: 32

Gnomad AFR AF: 0.677

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.558

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.449

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

GnomAD4 genome AF: 0.508 AC: 77139 AN: 151974 Hom.: 20568 Cov.: 32 AF XY: 0.509 AC XY: 37816 AN XY: 74308

Gnomad4 AFR AF: 0.678

Gnomad4 AMR AF: 0.455

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.366

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.558

Gnomad4 NFE AF: 0.441

Gnomad4 OTH AF: 0.450

Alfa AF: 0.483 Hom.: 2481

Bravo AF: 0.506

Asia WGS AF: 0.372 AC: 1294 AN: 3472

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

May 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.47
DANN	Benign	0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2

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: rs6781853; hg19: chr3-171321314;