1-147655173-C-T

Position:

• chr1-147655173-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016361.5(ACP6):​c.635G>A​(p.Arg212Lys) 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. 14/20 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: ACP6 NM_016361.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0740

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]

ACP6 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056426138).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACP6	NM_016361.5	c.635G>A	p.Arg212Lys	missense_variant	5/10	ENST00000583509.7	NP_057445.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACP6	ENST00000583509.7	c.635G>A	p.Arg212Lys	missense_variant	5/10	1	NM_016361.5	ENSP00000463574.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 09, 2021

The c.635G>A (p.R212K) alteration is located in exon 5 (coding exon 5) of the ACP6 gene. This alteration results from a G to A substitution at nucleotide position 635, causing the arginine (R) at amino acid position 212 to be replaced by a lysine (K). 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	0.085
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.6
DANN	Benign	0.76
DEOGEN2	Benign	0.039	T;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.62	T;T;T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.056	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.43	N;N;.
PrimateAI	Benign	0.34	T
REVEL	Benign	0.13
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0040	B;B;.
Vest4		0.059
MutPred		0.53		Gain of methylation at R212 (P = 0.0062);Gain of methylation at R212 (P = 0.0062);.;
MVP		0.23
ClinPred		0.094	T
GERP RS		-0.95
Varity_R		0.043
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: chr1-147127288;