NM_002662.5:c.3186G>A

Variant names:

• chr3-171603117-C-T
• rs6766336
• NM_002662.5:c.3186G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_002662.5(PLD1):​c.3186G>A​(p.Gly1062Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0182 in 1,613,854 control chromosomes in the GnomAD database, including 908 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.047 (414 hom., cov: 32)
  • Exomes 𝑓: 0.015 (494 hom.)
• Consequence: PLD1 NM_002662.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0930
• Publications: 6 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 3-171603117-C-T is Benign according to our data. Variant chr3-171603117-C-T is described in ClinVar as Benign. ClinVar VariationId is 1266999.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.093 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 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.3186G>A	p.Gly1062Gly	synonymous	Exon 27 of 27	NP_002653.1	Q13393-1
	PLD1	NM_001130081.3		c.3072G>A	p.Gly1024Gly	synonymous	Exon 26 of 26	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.3186G>A	p.Gly1062Gly	synonymous	Exon 27 of 27	ENSP00000342793.4	Q13393-1
	PLD1	ENST00000356327.9	TSL:1	c.3072G>A	p.Gly1024Gly	synonymous	Exon 26 of 26	ENSP00000348681.5	Q13393-2
	PLD1	ENST00000959555.1		c.3186G>A	p.Gly1062Gly	synonymous	Exon 27 of 27	ENSP00000629614.1

Frequencies

GnomAD3 genomes AF: 0.0471 AC: 7160 AN: 152070 Hom.: 413 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.0208

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.00396

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0133

Gnomad OTH AF: 0.0359

GnomAD2 exomes AF: 0.0177 AC: 4458 AN: 251216 AF XY: 0.0151

Gnomad AFR exome AF: 0.143

Gnomad AMR exome AF: 0.0128

Gnomad ASJ exome AF: 0.00258

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00376

Gnomad NFE exome AF: 0.0129

Gnomad OTH exome AF: 0.0108

GnomAD4 exome AF: 0.0152 AC: 22216 AN: 1461666 Hom.: 494 Cov.: 31 AF XY: 0.0143 AC XY: 10415 AN XY: 727134

African (AFR) AF: 0.146 AC: 4901 AN: 33470

American (AMR) AF: 0.0144 AC: 643 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00298 AC: 78 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00218 AC: 188 AN: 86256

European-Finnish (FIN) AF: 0.00392 AC: 209 AN: 53344

Middle Eastern (MID) AF: 0.0245 AC: 141 AN: 5766

European-Non Finnish (NFE) AF: 0.0134 AC: 14870 AN: 1111912

Other (OTH) AF: 0.0196 AC: 1186 AN: 60384

GnomAD4 genome AF: 0.0472 AC: 7176 AN: 152188 Hom.: 414 Cov.: 32 AF XY: 0.0452 AC XY: 3361 AN XY: 74424

African (AFR) AF: 0.140 AC: 5804 AN: 41492

American (AMR) AF: 0.0207 AC: 316 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4820

European-Finnish (FIN) AF: 0.00396 AC: 42 AN: 10600

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0133 AC: 907 AN: 68016

Other (OTH) AF: 0.0355 AC: 75 AN: 2112

Alfa AF: 0.0297 Hom.: 134

Bravo AF: 0.0528

Asia WGS AF: 0.0130 AC: 47 AN: 3478

EpiCase AF: 0.0130

EpiControl AF: 0.0123

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	5.5
DANN	Benign	0.67
PhyloP100		0.093
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: rs6766336; hg19: chr3-171320907;