1-147659522-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_016361.5(ACP6):c.353G>A(p.Gly118Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: ACP6 NM_016361.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.13

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.953

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACP6	NM_016361.5	c.353G>A	p.Gly118Asp	missense_variant	3/10	ENST00000583509.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACP6	ENST00000583509.7	c.353G>A	p.Gly118Asp	missense_variant	3/10	1	NM_016361.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461760 Hom.: 0 Cov.: 41 AF XY: 0.00000275 AC XY: 2 AN XY: 727184

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Dec 27, 2023

The c.353G>A (p.G118D) alteration is located in exon 3 (coding exon 3) of the ACP6 gene. This alteration results from a G to A substitution at nucleotide position 353, causing the glycine (G) at amino acid position 118 to be replaced by an aspartic acid (D). 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	0.19
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
Cadd	Uncertain	26
Dann	Uncertain	1.0
DEOGEN2	Benign	0.18	T;.;.;T
Eigen	Pathogenic	0.94
Eigen_PC	Pathogenic	0.89
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D;D;T;D
M_CAP	Benign	0.071	D
MetaRNN	Pathogenic	0.95	D;D;D;D
MetaSVM	Benign	-0.37	T
MutationAssessor	Uncertain	2.8	M;M;.;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.67	T
Sift4G	Uncertain	0.037	D;D;T;D
Polyphen		1.0	D;D;.;.
Vest4		0.95
MutPred		0.82		Gain of ubiquitination at K116 (P = 0.0571);Gain of ubiquitination at K116 (P = 0.0571);.;.;
MVP		0.80
ClinPred		0.98	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.73
gMVP		0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr1-147131637;