3-171612191-T-C

Position:

• chr3-171612191-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.2882+88A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0155 in 1,169,086 control chromosomes in the GnomAD database, including 435 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.036 (228 hom., cov: 32)
  • Exomes 𝑓: 0.012 (207 hom.)
• Consequence: PLD1 NM_002662.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.809

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=-0.83).
• BP6: Variant 3-171612191-T-C is Benign according to our data. Variant chr3-171612191-T-C is described in ClinVar as [Benign]. Clinvar id is 1226207.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLD1	NM_002662.5	c.2882+88A>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.2882+88A>G		intron_variant		1	NM_002662.5	ENSP00000342793	A1
PLD1	ENST00000356327.9	c.2768+88A>G		intron_variant		1		ENSP00000348681	P4
PLD1	ENST00000446289.1	c.670+88A>G		intron_variant		1		ENSP00000395556

Frequencies

GnomAD3 genomes AF: 0.0358 AC: 5452 AN: 152192 Hom.: 227 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0160

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00386

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0113

Gnomad OTH AF: 0.0253

GnomAD4 exome AF: 0.0124 AC: 12625 AN: 1016776 Hom.: 207 AF XY: 0.0117 AC XY: 6042 AN XY: 514534

Gnomad4 AFR exome AF: 0.107

Gnomad4 AMR exome AF: 0.0121

Gnomad4 ASJ exome AF: 0.00314

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00153

Gnomad4 FIN exome AF: 0.00391

Gnomad4 NFE exome AF: 0.0114

Gnomad4 OTH exome AF: 0.0156

GnomAD4 genome AF: 0.0358 AC: 5459 AN: 152310 Hom.: 228 Cov.: 32 AF XY: 0.0342 AC XY: 2545 AN XY: 74484

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.0159

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00386

Gnomad4 NFE AF: 0.0113

Gnomad4 OTH AF: 0.0251

Alfa AF: 0.0249 Hom.: 11

Bravo AF: 0.0400

Asia WGS AF: 0.00924 AC: 33 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 15, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.073
DANN	Benign	0.67

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: rs77851303; hg19: chr3-171329981;