3-171605084-T-C

Variant names:

• chr3-171605084-T-C
• rs2287577
• NM_002662.5:c.3000+215A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002662.5(PLD1):​c.3000+215A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 152,130 control chromosomes in the GnomAD database, including 7,062 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.29 (7062 hom., cov: 32)
• Consequence: PLD1 NM_002662.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.460
• Publications: 0 publications found

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]

PLD1 Gene-Disease associations (from GenCC):

• cardiac valvular defect, developmental

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• PLD1-related congenital heart disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 3-171605084-T-C is Benign according to our data. Variant chr3-171605084-T-C is described in ClinVar as Benign. ClinVar VariationId is 1231101.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002662.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLD1	NM_002662.5	MANE Select	c.3000+215A>G		intron	N/A	NP_002653.1	Q13393-1
	PLD1	NM_001130081.3		c.2886+215A>G		intron	N/A	NP_001123553.1	Q13393-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLD1	ENST00000351298.9	TSL:1 MANE Select	c.3000+215A>G		intron	N/A	ENSP00000342793.4	Q13393-1
	PLD1	ENST00000356327.9	TSL:1	c.2886+215A>G		intron	N/A	ENSP00000348681.5	Q13393-2
	PLD1	ENST00000959555.1		c.3000+215A>G		intron	N/A	ENSP00000629614.1

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43667 AN: 152012 Hom.: 7034 Cov.: 32

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.288 AC: 43746 AN: 152130 Hom.: 7062 Cov.: 32 AF XY: 0.290 AC XY: 21583 AN XY: 74368

African (AFR) AF: 0.411 AC: 17056 AN: 41478

American (AMR) AF: 0.316 AC: 4837 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 664 AN: 3472

East Asian (EAS) AF: 0.238 AC: 1231 AN: 5176

South Asian (SAS) AF: 0.110 AC: 529 AN: 4824

European-Finnish (FIN) AF: 0.348 AC: 3674 AN: 10570

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.221 AC: 14997 AN: 68004

Other (OTH) AF: 0.247 AC: 521 AN: 2110

Alfa AF: 0.252 Hom.: 1945

Bravo AF: 0.293

Asia WGS AF: 0.181 AC: 631 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.52
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2287577; hg19: chr3-171322874;