3-171605515-T-C

Position:

• chr3-171605515-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002662.5(PLD1):​c.2883-99A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 721,512 control chromosomes in the GnomAD database, including 13,853 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2372 hom., cov: 32)
  • Exomes 𝑓: 0.19 (11481 hom.)
• Consequence: PLD1 NM_002662.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.270

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 3-171605515-T-C is Benign according to our data. Variant chr3-171605515-T-C is described in ClinVar as [Benign]. Clinvar id is 1227644.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLD1	NM_002662.5	c.2883-99A>G		intron_variant		ENST00000351298.9	NP_002653.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLD1	ENST00000351298.9	c.2883-99A>G		intron_variant		1	NM_002662.5	ENSP00000342793	A1
PLD1	ENST00000356327.9	c.2769-99A>G		intron_variant		1		ENSP00000348681	P4

Frequencies

GnomAD3 genomes AF: 0.171 AC: 26042 AN: 152066 Hom.: 2370 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.172

GnomAD4 exome AF: 0.195 AC: 110950 AN: 569328 Hom.: 11481 AF XY: 0.198 AC XY: 60476 AN XY: 306206

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.0838

Gnomad4 ASJ exome AF: 0.165

Gnomad4 EAS exome AF: 0.135

Gnomad4 SAS exome AF: 0.230

Gnomad4 FIN exome AF: 0.211

Gnomad4 NFE exome AF: 0.209

Gnomad4 OTH exome AF: 0.183

GnomAD4 genome AF: 0.171 AC: 26046 AN: 152184 Hom.: 2372 Cov.: 32 AF XY: 0.172 AC XY: 12768 AN XY: 74394

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.126

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.170

Alfa AF: 0.189 Hom.: 376

Bravo AF: 0.159

Asia WGS AF: 0.167 AC: 578 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 14, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.84

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

Publications

LitVar

Other links and lift over

dbSNP: rs2287578; hg19: chr3-171323305; COSMIC: COSV60576127; COSMIC: COSV60576127;