rs4254419

Variant names:

• chr19-40366127-T-A
• rs4254419
• NM_012268.4:c.-66+197T>A

Your query was ambiguous. Multiple possible variants found:

• chr19-40366127-T-A
• chr19-40366127-T-C
• chr19-40366127-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012268.4(PLD3):​c.-66+197T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 27)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PLD3 NM_012268.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.919
• Publications: 5 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLD3	NM_012268.4	c.-66+197T>A		intron_variant	Intron 2 of 12	ENST00000409735.9	NP_036400.2
PLD3	NM_001031696.4	c.-65-292T>A		intron_variant	Intron 2 of 12		NP_001026866.1
PLD3	NM_001291311.2	c.-66+197T>A		intron_variant	Intron 2 of 12		NP_001278240.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLD3	ENST00000409735.9	c.-66+197T>A		intron_variant	Intron 2 of 12	1	NM_012268.4	ENSP00000386938.3

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 211382 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 112962

African (AFR) AF: 0.00 AC: 0 AN: 4608

American (AMR) AF: 0.00 AC: 0 AN: 7134

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6202

East Asian (EAS) AF: 0.00 AC: 0 AN: 8660

South Asian (SAS) AF: 0.00 AC: 0 AN: 31348

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 11508

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 918

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 129042

Other (OTH) AF: 0.00 AC: 0 AN: 11962

GnomAD4 genome Cov.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.2
DANN	Benign	0.57
PhyloP100		0.92
PromoterAI		-0.048	Neutral

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: rs4254419; hg19: chr19-40872034;