3-171603180-AC-GT

Variant names:

• chr3-171603180-AC-GT
• NM_002662.5:c.3122_3123delGTinsAC
• PLD1 p.Arg1041His

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_002662.5(PLD1):​c.3122_3123delGTinsAC​(p.Arg1041His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLD1 NM_002662.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.30
• Publications: 0 publications found

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]

PLD1 Gene-Disease associations (from GenCC):

• cardiac valvular defect, developmental

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• PLD1-related congenital heart disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002662.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLD1	NM_002662.5	MANE Select	c.3122_3123delGTinsAC	p.Arg1041His	missense	N/A	NP_002653.1	Q13393-1
	PLD1	NM_001130081.3		c.3008_3009delGTinsAC	p.Arg1003His	missense	N/A	NP_001123553.1	Q13393-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLD1	ENST00000351298.9	TSL:1 MANE Select	c.3122_3123delGTinsAC	p.Arg1041His	missense	N/A	ENSP00000342793.4	Q13393-1
	PLD1	ENST00000356327.9	TSL:1	c.3008_3009delGTinsAC	p.Arg1003His	missense	N/A	ENSP00000348681.5	Q13393-2
	PLD1	ENST00000959555.1		c.3122_3123delGTinsAC	p.Arg1041His	missense	N/A	ENSP00000629614.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-171320970;