17-17206004-C-G

Variant names:

• chr17-17206004-C-G
• rs773687737
• NM_178836.4:c.283G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_178836.4(PLD6):​c.283G>C​(p.Asp95His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,396,190 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D95Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PLD6 NM_178836.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.48
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.283G>C	p.Asp95His	missense	Exon 1 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.283G>C	p.Asp95His	missense	Exon 1 of 2	ENSP00000317177.3	Q8N2A8
	ENSG00000264187	ENST00000427497.3	TSL:1	n.*417+1021G>C		intron	N/A	ENSP00000394249.3	J3QW42
	MPRIP	ENST00000578209.5	TSL:3	c.*17+4371C>G		intron	N/A	ENSP00000464276.1	J3QRL2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000141 AC: 2 AN: 141712 AF XY: 0.0000258

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1396190 Hom.: 0 Cov.: 32 AF XY: 0.00000290 AC XY: 2 AN XY: 689476

African (AFR) AF: 0.00 AC: 0 AN: 31706

American (AMR) AF: 0.00 AC: 0 AN: 36306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25106

East Asian (EAS) AF: 0.00 AC: 0 AN: 36092

South Asian (SAS) AF: 0.0000251 AC: 2 AN: 79536

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5358

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1081666

Other (OTH) AF: 0.00 AC: 0 AN: 58066

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000188 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.49
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.074	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.36	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		2.5
PrimateAI	Pathogenic	0.93	D
PROVEAN	Pathogenic	-5.2	D
REVEL	Benign	0.19
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0070	D
Polyphen		1.0	D
Vest4		0.36
MutPred		0.45		Loss of sheet (P = 0.0457)
MVP		0.30
MPC		1.6
ClinPred		0.86	D
GERP RS		4.3
PromoterAI		-0.13	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.77
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs773687737; hg19: chr17-17109318;