chr17-17202867-T-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 15/22 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
• Publications: 0 publications found

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

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

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178836.4. 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
	PLD6	NM_178836.4	MANE Select	c.659A>G	p.Lys220Arg	missense	Exon 2 of 2	NP_849158.2	Q8N2A8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLD6	ENST00000321560.4	TSL:1 MANE Select	c.659A>G	p.Lys220Arg	missense	Exon 2 of 2	ENSP00000317177.3	Q8N2A8
	ENSG00000264187	ENST00000427497.3	TSL:1	n.*686A>G		non_coding_transcript_exon	Exon 12 of 12	ENSP00000394249.3	J3QW42
	ENSG00000264187	ENST00000427497.3	TSL:1	n.*686A>G		3_prime_UTR	Exon 12 of 12	ENSP00000394249.3	J3QW42

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		4.2
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

Other links and lift over

hg19: chr17-17106181;