NM_016361.5:c.652C>G

Variant names:

• chr1-147654322-G-C
• rs140566115
• NM_016361.5:c.652C>G

Variant summary

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

The NM_016361.5(ACP6):​c.652C>G​(p.Arg218Gly) variant causes a missense 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. 12/20 in silico tools predict a benign outcome for this variant. 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. R218W) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ACP6 NM_016361.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.39

Genes affected

ACP6 (HGNC:29609): (acid phosphatase 6, lysophosphatidic) This gene encodes a member of the histidine acid phosphatase protein family. The encoded protein hydrolyzes lysophosphatidic acid, which is involved in G protein-coupled receptor signaling, lipid raft modulation, and in balancing lipid composition within the cell. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2016]

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=0.18273196).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACP6	NM_016361.5	c.652C>G	p.Arg218Gly	missense_variant	Exon 6 of 10	ENST00000583509.7	NP_057445.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACP6	ENST00000583509.7	c.652C>G	p.Arg218Gly	missense_variant	Exon 6 of 10	1	NM_016361.5	ENSP00000463574.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.084	T;.;.
Eigen	Benign	-0.061
Eigen_PC	Benign	0.046
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.84	T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M;M;.
PrimateAI	Benign	0.36	T
REVEL	Benign	0.046
Sift4G	Benign	0.14	T;T;T
Polyphen		0.20	B;B;.
Vest4		0.21
MutPred		0.45		Loss of methylation at R218 (P = 0.0355);Loss of methylation at R218 (P = 0.0355);.;
MVP		0.40
ClinPred		0.49	T
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.53
gMVP		0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs140566115; hg19: chr1-147126437;