rs144959805

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM2PM5BP4_Moderate

The NM_016361.5(ACP6):​c.379G>T​(p.Val127Leu) 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. 13/20 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. V127M) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 33)

Consequence

ACP6
NM_016361.5 missense

Scores

1
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.13
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM5
Other missense variant is known to change same aminoacid residue: Variant chr1-147659496-C-T is described in Lovd as [Likely_pathogenic].
BP4
Computational evidence support a benign effect (MetaRNN=0.24794012).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ACP6NM_016361.5 linkuse as main transcriptc.379G>T p.Val127Leu missense_variant 3/10 ENST00000583509.7 NP_057445.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ACP6ENST00000583509.7 linkuse as main transcriptc.379G>T p.Val127Leu missense_variant 3/101 NM_016361.5 ENSP00000463574 P1Q9NPH0-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251342
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135852
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
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
Cov.:
42
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
20
DANN
Uncertain
0.98
DEOGEN2
Benign
0.059
T;.;.;T
Eigen
Benign
-0.22
Eigen_PC
Benign
-0.038
FATHMM_MKL
Benign
0.71
D
LIST_S2
Benign
0.75
T;T;D;T
M_CAP
Benign
0.0066
T
MetaRNN
Benign
0.25
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.3
L;L;.;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Benign
0.42
T
REVEL
Benign
0.046
Sift4G
Benign
0.20
T;T;T;T
Polyphen
0.040
B;B;.;.
Vest4
0.21
MutPred
0.53
Loss of methylation at K126 (P = 0.035);Loss of methylation at K126 (P = 0.035);.;.;
MVP
0.26
ClinPred
0.59
D
GERP RS
4.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.26
gMVP
0.49

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: rs144959805; hg19: chr1-147131611; API