1-147652546-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_016361.5(ACP6):​c.784C>T​(p.His262Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,804 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: 30)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

ACP6
NM_016361.5 missense

Scores

3
9
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.59
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.857

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ACP6NM_016361.5 linkuse as main transcriptc.784C>T p.His262Tyr missense_variant 7/10 ENST00000583509.7 NP_057445.4 Q9NPH0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ACP6ENST00000583509.7 linkuse as main transcriptc.784C>T p.His262Tyr missense_variant 7/101 NM_016361.5 ENSP00000463574.1 Q9NPH0-1

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251332
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135844
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS 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:
0.00000410
AC:
6
AN:
1461804
Hom.:
0
Cov.:
35
AF XY:
0.00000275
AC XY:
2
AN XY:
727204
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
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.:
30

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 30, 2024The c.784C>T (p.H262Y) alteration is located in exon 7 (coding exon 7) of the ACP6 gene. This alteration results from a C to T substitution at nucleotide position 784, causing the histidine (H) at amino acid position 262 to be replaced by a tyrosine (Y). 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
Uncertain
0.36
BayesDel_addAF
Uncertain
0.086
D
BayesDel_noAF
Uncertain
0.070
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.16
T
Eigen
Uncertain
0.66
Eigen_PC
Uncertain
0.54
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.89
D
M_CAP
Benign
0.050
D
MetaRNN
Pathogenic
0.86
D
MetaSVM
Benign
-0.54
T
MutationAssessor
Pathogenic
3.1
M
PrimateAI
Uncertain
0.52
T
Sift4G
Uncertain
0.011
D
Polyphen
1.0
D
Vest4
0.84
MutPred
0.62
Loss of catalytic residue at L264 (P = 0.0589);
MVP
0.77
ClinPred
0.98
D
GERP RS
5.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.82
gMVP
0.88

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs781793007; hg19: chr1-147124349; API