chr3-171636574-T-C

Position:

• chr3-171636574-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLD1	NM_002662.5	c.2593+6266A>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.2593+6266A>G		intron_variant		1	NM_002662.5	ENSP00000342793	A1

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

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.170

Alfa AF: 0.200 Hom.: 1447

Bravo AF: 0.164

Asia WGS AF: 0.165 AC: 570 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	6.6
DANN	Benign	0.59

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: rs9863761; hg19: chr3-171354364;