rs10407447

Variant names:

• chr19-40363275-A-G
• rs10407447
• NM_012268.4:c.-278-2443A>G

Your query was ambiguous. Multiple possible variants found:

• chr19-40363275-A-G
• chr19-40363275-A-T

Variant summary

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

The NM_012268.4(PLD3):​c.-278-2443A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,080 control chromosomes in the GnomAD database, including 3,059 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 0.20 (3059 hom., cov: 32)
• Consequence: PLD3 NM_012268.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.284
• Publications: 14 publications found

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]

PLD3 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia 46

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012268.4. 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
	PLD3	NM_012268.4	MANE Select	c.-278-2443A>G		intron	N/A	NP_036400.2
	PLD3	NM_001031696.4		c.-98-2278A>G		intron	N/A	NP_001026866.1
	PLD3	NM_001291311.2		c.-278-2443A>G		intron	N/A	NP_001278240.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLD3	ENST00000409735.9	TSL:1 MANE Select	c.-278-2443A>G		intron	N/A	ENSP00000386938.3
	PLD3	ENST00000356508.9	TSL:1	c.-98-2278A>G		intron	N/A	ENSP00000348901.5
	PLD3	ENST00000409281.5	TSL:2	c.-278-2443A>G		intron	N/A	ENSP00000387022.1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29790 AN: 151962 Hom.: 3060 Cov.: 32

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.0473

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.195

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

GnomAD4 genome AF: 0.196 AC: 29807 AN: 152080 Hom.: 3059 Cov.: 32 AF XY: 0.196 AC XY: 14604 AN XY: 74338

African (AFR) AF: 0.261 AC: 10823 AN: 41454

American (AMR) AF: 0.206 AC: 3153 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 843 AN: 3468

East Asian (EAS) AF: 0.149 AC: 771 AN: 5178

South Asian (SAS) AF: 0.0467 AC: 225 AN: 4818

European-Finnish (FIN) AF: 0.203 AC: 2148 AN: 10574

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11134 AN: 67990

Other (OTH) AF: 0.191 AC: 405 AN: 2116

Alfa AF: 0.172 Hom.: 7299

Bravo AF: 0.203

Asia WGS AF: 0.100 AC: 347 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.0
DANN	Benign	0.79
PhyloP100		0.28
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: rs10407447; hg19: chr19-40869182;