chr1-147647504-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016361.5(ACP6):​c.1206G>A​(p.Met402Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000805 in 1,614,024 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M402V) has been classified as Benign.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

ACP6
NM_016361.5 missense

Scores

16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.166
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 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=0.03343427).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ACP6NM_016361.5 linkuse as main transcriptc.1206G>A p.Met402Ile missense_variant 10/10 ENST00000583509.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ACP6ENST00000583509.7 linkuse as main transcriptc.1206G>A p.Met402Ile missense_variant 10/101 NM_016361.5 P1Q9NPH0-1
ACP6ENST00000613673.4 linkuse as main transcriptn.4428G>A non_coding_transcript_exon_variant 8/81
ACP6ENST00000609196.5 linkuse as main transcriptc.460+2639G>A intron_variant 3
ACP6ENST00000460583.1 linkuse as main transcriptn.769G>A non_coding_transcript_exon_variant 3/32

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152196
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000962
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000398
AC:
10
AN:
251384
Hom.:
0
AF XY:
0.0000368
AC XY:
5
AN XY:
135868
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000544
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:
0.00000547
AC:
8
AN:
1461828
Hom.:
0
Cov.:
33
AF XY:
0.00000550
AC XY:
4
AN XY:
727224
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000151
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152196
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000962
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000416
ExAC
AF:
0.0000247
AC:
3

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 GeneticsApr 17, 2023The c.1206G>A (p.M402I) alteration is located in exon 10 (coding exon 10) of the ACP6 gene. This alteration results from a G to A substitution at nucleotide position 1206, causing the methionine (M) at amino acid position 402 to be replaced by an isoleucine (I). 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
Benign
-0.56
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
10
DANN
Benign
0.92
DEOGEN2
Benign
0.071
T
Eigen
Benign
-0.53
Eigen_PC
Benign
-0.45
FATHMM_MKL
Benign
0.48
N
LIST_S2
Benign
0.66
T
M_CAP
Benign
0.0091
T
MetaRNN
Benign
0.033
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.69
N
MutationTaster
Benign
0.83
N
PrimateAI
Benign
0.31
T
Sift4G
Benign
0.30
T
Polyphen
0.0020
B
Vest4
0.052
MutPred
0.43
Gain of loop (P = 0.0851);
MVP
0.24
ClinPred
0.039
T
GERP RS
2.7
Varity_R
0.14
gMVP
0.65

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: rs782505855; hg19: chr1-147119306; API