3-171603219-T-C

Variant names:

• chr3-171603219-T-C
• rs75970900
• NM_002662.5:c.3084A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_002662.5(PLD1):​c.3084A>G​(p.Glu1028Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00221 in 1,614,076 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0096 (10 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (24 hom.)
• Consequence: PLD1 NM_002662.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.148
• Publications: 4 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 (BayesDel_noAF=-0.61).
• BP6: Variant 3-171603219-T-C is Benign according to our data. Variant chr3-171603219-T-C is described in ClinVar as Benign. ClinVar VariationId is 775926.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.148 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0096 (1462/152322) while in subpopulation AFR AF = 0.0323 (1344/41570). AF 95% confidence interval is 0.0309. There are 10 homozygotes in GnomAd4. There are 684 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

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.3084A>G	p.Glu1028Glu	synonymous	Exon 27 of 27	NP_002653.1	Q13393-1
	PLD1	NM_001130081.3		c.2970A>G	p.Glu990Glu	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.3084A>G	p.Glu1028Glu	synonymous	Exon 27 of 27	ENSP00000342793.4	Q13393-1
	PLD1	ENST00000356327.9	TSL:1	c.2970A>G	p.Glu990Glu	synonymous	Exon 26 of 26	ENSP00000348681.5	Q13393-2
	PLD1	ENST00000959555.1		c.3084A>G	p.Glu1028Glu	synonymous	Exon 27 of 27	ENSP00000629614.1

Frequencies

GnomAD3 genomes AF: 0.00958 AC: 1458 AN: 152204 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.0323

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00425

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.00573

GnomAD2 exomes AF: 0.00306 AC: 769 AN: 251144 AF XY: 0.00246

Gnomad AFR exome AF: 0.0338

Gnomad AMR exome AF: 0.00356

Gnomad ASJ exome AF: 0.00159

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000520

Gnomad OTH exome AF: 0.00229

GnomAD4 exome AF: 0.00144 AC: 2108 AN: 1461754 Hom.: 24 Cov.: 31 AF XY: 0.00131 AC XY: 955 AN XY: 727204

African (AFR) AF: 0.0351 AC: 1174 AN: 33472

American (AMR) AF: 0.00374 AC: 167 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00180 AC: 47 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000417 AC: 36 AN: 86258

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53404

Middle Eastern (MID) AF: 0.0128 AC: 74 AN: 5768

European-Non Finnish (NFE) AF: 0.000373 AC: 415 AN: 1111928

Other (OTH) AF: 0.00318 AC: 192 AN: 60388

GnomAD4 genome AF: 0.00960 AC: 1462 AN: 152322 Hom.: 10 Cov.: 32 AF XY: 0.00918 AC XY: 684 AN XY: 74486

African (AFR) AF: 0.0323 AC: 1344 AN: 41570

American (AMR) AF: 0.00425 AC: 65 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10624

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.000368 AC: 25 AN: 68024

Other (OTH) AF: 0.00567 AC: 12 AN: 2116

Alfa AF: 0.00475 Hom.: 6

Bravo AF: 0.0108

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.000927

EpiControl AF: 0.000711

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	5.9
DANN	Benign	0.58
PhyloP100		-0.15
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	polymorphism

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: rs75970900; hg19: chr3-171321009;