3-171677678-A-G

Variant names:

• chr3-171677678-A-G
• rs2124147
• NM_002662.5:c.1884T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002662.5(PLD1):​c.1884T>C​(p.Arg628Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 1,612,886 control chromosomes in the GnomAD database, including 168,178 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (20667 hom., cov: 32)
  • Exomes 𝑓: 0.45 (147511 hom.)
• Consequence: PLD1 NM_002662.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.705
• Publications: 25 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.012).
• BP6: Variant 3-171677678-A-G is Benign according to our data. Variant chr3-171677678-A-G is described in ClinVar as Benign. ClinVar VariationId is 1276405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.705 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.673 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.1884T>C	p.Arg628Arg	synonymous	Exon 17 of 27	NP_002653.1	Q13393-1
	PLD1	NM_001130081.3		c.1770T>C	p.Arg590Arg	synonymous	Exon 16 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.1884T>C	p.Arg628Arg	synonymous	Exon 17 of 27	ENSP00000342793.4	Q13393-1
	PLD1	ENST00000356327.9	TSL:1	c.1770T>C	p.Arg590Arg	synonymous	Exon 16 of 26	ENSP00000348681.5	Q13393-2
	PLD1	ENST00000959555.1		c.1884T>C	p.Arg628Arg	synonymous	Exon 17 of 27	ENSP00000629614.1

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77081 AN: 151874 Hom.: 20619 Cov.: 32

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.445

GnomAD2 exomes AF: 0.444 AC: 111545 AN: 251108 AF XY: 0.435

Gnomad AFR exome AF: 0.685

Gnomad AMR exome AF: 0.473

Gnomad ASJ exome AF: 0.352

Gnomad EAS exome AF: 0.350

Gnomad FIN exome AF: 0.542

Gnomad NFE exome AF: 0.434

Gnomad OTH exome AF: 0.413

GnomAD4 exome AF: 0.446 AC: 650829 AN: 1460894 Hom.: 147511 Cov.: 35 AF XY: 0.441 AC XY: 320364 AN XY: 726828

African (AFR) AF: 0.691 AC: 23127 AN: 33468

American (AMR) AF: 0.465 AC: 20764 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 9108 AN: 26116

East Asian (EAS) AF: 0.345 AC: 13668 AN: 39670

South Asian (SAS) AF: 0.350 AC: 30153 AN: 86214

European-Finnish (FIN) AF: 0.537 AC: 28674 AN: 53398

Middle Eastern (MID) AF: 0.337 AC: 1944 AN: 5762

European-Non Finnish (NFE) AF: 0.448 AC: 497532 AN: 1111242

Other (OTH) AF: 0.428 AC: 25859 AN: 60352

GnomAD4 genome AF: 0.508 AC: 77183 AN: 151992 Hom.: 20667 Cov.: 32 AF XY: 0.508 AC XY: 37767 AN XY: 74294

African (AFR) AF: 0.680 AC: 28185 AN: 41446

American (AMR) AF: 0.456 AC: 6968 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 1173 AN: 3472

East Asian (EAS) AF: 0.327 AC: 1692 AN: 5170

South Asian (SAS) AF: 0.347 AC: 1671 AN: 4812

European-Finnish (FIN) AF: 0.553 AC: 5831 AN: 10546

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.444 AC: 30192 AN: 67966

Other (OTH) AF: 0.445 AC: 939 AN: 2108

Alfa AF: 0.451 Hom.: 50761

Bravo AF: 0.506

Asia WGS AF: 0.361 AC: 1258 AN: 3478

EpiCase AF: 0.423

EpiControl AF: 0.420

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	-0.49
CADD	Benign	8.1
DANN	Benign	0.93
PhyloP100		0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=93/7	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2124147; hg19: chr3-171395468; COSMIC: COSV60566349; COSMIC: COSV60566349;