3-171605409-G-A

Variant names:

• chr3-171605409-G-A
• rs557980910
• NM_002662.5:c.2890C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002662.5(PLD1):​c.2890C>T​(p.Leu964Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000512 in 1,601,250 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (1 hom., cov: 33)
  • Exomes 𝑓: 0.000050 (0 hom.)
• Consequence: PLD1 NM_002662.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.71
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07752684).

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.2890C>T	p.Leu964Phe	missense	Exon 26 of 27	NP_002653.1	Q13393-1
	PLD1	NM_001130081.3		c.2776C>T	p.Leu926Phe	missense	Exon 25 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.2890C>T	p.Leu964Phe	missense	Exon 26 of 27	ENSP00000342793.4	Q13393-1
	PLD1	ENST00000356327.9	TSL:1	c.2776C>T	p.Leu926Phe	missense	Exon 25 of 26	ENSP00000348681.5	Q13393-2
	PLD1	ENST00000959555.1		c.2890C>T	p.Leu964Phe	missense	Exon 26 of 27	ENSP00000629614.1

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152094 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000251 AC: 63 AN: 251062 AF XY: 0.000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00180

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000497 AC: 72 AN: 1449038 Hom.: 0 Cov.: 27 AF XY: 0.0000485 AC XY: 35 AN XY: 721690

African (AFR) AF: 0.00 AC: 0 AN: 33200

American (AMR) AF: 0.00159 AC: 71 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26070

East Asian (EAS) AF: 0.00 AC: 0 AN: 39622

South Asian (SAS) AF: 0.00 AC: 0 AN: 85968

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5732

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1100424

Other (OTH) AF: 0.0000167 AC: 1 AN: 59916

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152212 Hom.: 1 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74432

African (AFR) AF: 0.00 AC: 0 AN: 41542

American (AMR) AF: 0.000654 AC: 10 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000117

ExAC AF: 0.000198 AC: 24

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		5.7
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.20
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.016	D
Polyphen		0.34	B
Vest4		0.56
MutPred		0.51		Gain of MoRF binding (P = 0.1643)
MVP		0.69
MPC		0.18
ClinPred		0.12	T
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.70
gMVP		0.75
Mutation Taster		=17/83	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs557980910; hg19: chr3-171323199;