19-40366695-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_012268.4(PLD3):c.102+11T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000161 in 1,611,530 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00060 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: PLD3 NM_012268.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.46

Genes affected

PLD3 (HGNC:17158): (phospholipase D family member 3) This gene encodes a member of the phospholipase D (PLD) family of enzymes that catalyze the hydrolysis of membrane phospholipids. The encoded protein is a single-pass type II membrane protein and contains two PLD phosphodiesterase domains. This protein influences processing of amyloid-beta precursor protein. Mutations in this gene are associated with Alzheimer disease risk. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Apr 2014]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 19-40366695-T-G is Benign according to our data. Variant chr19-40366695-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 1992157.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 92 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLD3	NM_012268.4	c.102+11T>G		intron_variant		ENST00000409735.9
PLD3	NM_001031696.4	c.102+11T>G		intron_variant
PLD3	NM_001291311.2	c.102+11T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLD3	ENST00000409735.9	c.102+11T>G		intron_variant		1	NM_012268.4	P1

Frequencies

GnomAD3 genomes AF: 0.000605 AC: 92 AN: 152124 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.000249 AC: 62 AN: 249314 Hom.: 0 AF XY: 0.000134 AC XY: 18 AN XY: 134764

Gnomad AFR exome AF: 0.00117

Gnomad AMR exome AF: 0.000731

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000888

Gnomad OTH exome AF: 0.00132

GnomAD4 exome AF: 0.000114 AC: 167 AN: 1459288 Hom.: 0 Cov.: 31 AF XY: 0.0000992 AC XY: 72 AN XY: 725692

Gnomad4 AFR exome AF: 0.00141

Gnomad4 AMR exome AF: 0.000833

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000567

Gnomad4 OTH exome AF: 0.000299

GnomAD4 genome AF: 0.000604 AC: 92 AN: 152242 Hom.: 1 Cov.: 32 AF XY: 0.000672 AC XY: 50 AN XY: 74442

Gnomad4 AFR AF: 0.00142

Gnomad4 AMR AF: 0.00144

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000356 Hom.: 0

Bravo AF: 0.000574

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 22, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	0.40
Dann	Benign	0.79

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: rs201086671; hg19: chr19-40872602;