chr1-147659496-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PP5_ModerateBP4BS2_Supporting

The NM_016361.5(ACP6):​c.379G>A​(p.Val127Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000899 in 1,614,212 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: 𝑓 0.00044 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00095 ( 2 hom. )

Consequence

ACP6
NM_016361.5 missense

Scores

1
4
12

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PP5
Variant 1-147659496-C-T is Pathogenic according to our data. Variant chr1-147659496-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 224824.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-147659496-C-T is described in Lovd as [Likely_pathogenic].
BP4
Computational evidence support a benign effect (MetaRNN=0.10326934). . Strength limited to SUPPORTING due to the PP5.
BS2
High Homozygotes in GnomAdExome4 at 2 AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ACP6NM_016361.5 linkc.379G>A p.Val127Met missense_variant Exon 3 of 10 ENST00000583509.7 NP_057445.4 Q9NPH0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ACP6ENST00000583509.7 linkc.379G>A p.Val127Met missense_variant Exon 3 of 10 1 NM_016361.5 ENSP00000463574.1 Q9NPH0-1

Frequencies

GnomAD3 genomes
AF:
0.000440
AC:
67
AN:
152226
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000145
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000897
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000382
AC:
96
AN:
251342
Hom.:
0
AF XY:
0.000375
AC XY:
51
AN XY:
135852
show subpopulations
Gnomad AFR exome
AF:
0.000246
Gnomad AMR exome
AF:
0.00
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:
0.000801
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000947
AC:
1384
AN:
1461868
Hom.:
2
Cov.:
42
AF XY:
0.000921
AC XY:
670
AN XY:
727236
show subpopulations
Gnomad4 AFR exome
AF:
0.000209
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.00122
Gnomad4 OTH exome
AF:
0.000348
GnomAD4 genome
AF:
0.000440
AC:
67
AN:
152344
Hom.:
0
Cov.:
33
AF XY:
0.000403
AC XY:
30
AN XY:
74498
show subpopulations
Gnomad4 AFR
AF:
0.000144
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000897
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000754
Hom.:
0
Bravo
AF:
0.000423
TwinsUK
AF:
0.00243
AC:
9
ALSPAC
AF:
0.00182
AC:
7
ESP6500AA
AF:
0.000454
AC:
2
ESP6500EA
AF:
0.00105
AC:
9
ExAC
AF:
0.000428
AC:
52
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000382
EpiControl
AF:
0.000356

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Cerebral visual impairment and intellectual disability Pathogenic:1
Likely pathogenic, criteria provided, single submitterresearchLupski Lab, Baylor-Hopkins CMG, Baylor College of MedicineSep 09, 2015This study shows that diverse genetic causes underlie CVI. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.35
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.077
T;.;.;T
Eigen
Uncertain
0.52
Eigen_PC
Uncertain
0.48
FATHMM_MKL
Benign
0.66
D
LIST_S2
Benign
0.78
T;T;D;D
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.10
T;T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Pathogenic
3.0
M;M;.;.
PrimateAI
Benign
0.44
T
REVEL
Benign
0.18
Sift4G
Uncertain
0.0050
D;D;D;D
Polyphen
0.99
D;D;.;.
Vest4
0.44
MVP
0.40
ClinPred
0.74
D
GERP RS
4.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.22
gMVP
0.48

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