17-17202867-T-C

Variant names:

• chr17-17202867-T-C
• NM_178836.4:c.659A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178836.4(PLD6):​c.659A>G​(p.Lys220Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLD6 NM_178836.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.16

Genes affected

PLD6 (HGNC:30447): (phospholipase D family member 6) Enables cardiolipin hydrolase activity and protein homodimerization activity. Involved in mitochondrial fusion. Acts upstream of or within positive regulation of mitochondrial fusion. Located in mitochondrial outer membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000264187 (HGNC:):

MPRIP (HGNC:30321): (myosin phosphatase Rho interacting protein) Enables cadherin binding activity. Predicted to be involved in actin filament organization. Located in actin cytoskeleton and cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.075915575).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLD6	NM_178836.4	c.659A>G	p.Lys220Arg	missense_variant	Exon 2 of 2	ENST00000321560.4	NP_849158.2
PLD6	XM_017024310.3	c.655A>G	p.Arg219Gly	missense_variant	Exon 2 of 2		XP_016879799.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLD6	ENST00000321560.4	c.659A>G	p.Lys220Arg	missense_variant	Exon 2 of 2	1	NM_178836.4	ENSP00000317177.3
ENSG00000264187	ENST00000427497.3	n.*686A>G		non_coding_transcript_exon_variant	Exon 12 of 12	1		ENSP00000394249.3
ENSG00000264187	ENST00000427497.3	n.*686A>G		3_prime_UTR_variant	Exon 12 of 12	1		ENSP00000394249.3
MPRIP	ENST00000578209.5	c.*17+1234T>C		intron_variant	Intron 5 of 5	3		ENSP00000464276.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 10, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.659A>G (p.K220R) alteration is located in exon 2 (coding exon 2) of the PLD6 gene. This alteration results from a A to G substitution at nucleotide position 659, causing the lysine (K) at amino acid position 220 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	15
DANN	Benign	0.95
DEOGEN2	Benign	0.057	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.027
Sift	Benign	0.075	T
Sift4G	Benign	0.17	T
Polyphen		0.016	B
Vest4		0.079
MutPred		0.37		Loss of methylation at K220 (P = 0.003);
MVP		0.095
MPC		0.44
ClinPred		0.14	T
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.041
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-17106181;