chr3-171636574-T-C

Variant names:

• chr3-171636574-T-C
• rs9863761
• NM_002662.5:c.2593+6266A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002662.5(PLD1):​c.2593+6266A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,046 control chromosomes in the GnomAD database, including 2,418 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (2418 hom., cov: 31)
• Consequence: PLD1 NM_002662.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800
• 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, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.224 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLD1	NM_002662.5	MANE Select	c.2593+6266A>G		intron	N/A	NP_002653.1
	PLD1	NM_001130081.3		c.2479+6266A>G		intron	N/A	NP_001123553.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLD1	ENST00000351298.9	TSL:1 MANE Select	c.2593+6266A>G		intron	N/A	ENSP00000342793.4
	PLD1	ENST00000356327.9	TSL:1	c.2479+6266A>G		intron	N/A	ENSP00000348681.5
	PLD1	ENST00000446289.1	TSL:1	c.379+6266A>G		intron	N/A	ENSP00000395556.1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26528 AN: 151928 Hom.: 2415 Cov.: 31

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.172

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

GnomAD4 genome AF: 0.175 AC: 26538 AN: 152046 Hom.: 2418 Cov.: 31 AF XY: 0.175 AC XY: 13009 AN XY: 74318

African (AFR) AF: 0.133 AC: 5516 AN: 41512

American (AMR) AF: 0.119 AC: 1821 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 508 AN: 3464

East Asian (EAS) AF: 0.127 AC: 659 AN: 5188

South Asian (SAS) AF: 0.236 AC: 1134 AN: 4814

European-Finnish (FIN) AF: 0.204 AC: 2157 AN: 10548

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14096 AN: 67938

Other (OTH) AF: 0.170 AC: 359 AN: 2112

Alfa AF: 0.199 Hom.: 1601

Bravo AF: 0.164

Asia WGS AF: 0.165 AC: 570 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	6.6
DANN	Benign	0.59
PhyloP100		-0.080
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: rs9863761; hg19: chr3-171354364;