chr1-147647445-A-G

Variant summary

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

The NM_016361.5(ACP6):ā€‹c.1265T>Cā€‹(p.Met422Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,782 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 (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

ACP6
NM_016361.5 missense

Scores

16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.227
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=0.06500682).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ACP6NM_016361.5 linkuse as main transcriptc.1265T>C p.Met422Thr missense_variant 10/10 ENST00000583509.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ACP6ENST00000583509.7 linkuse as main transcriptc.1265T>C p.Met422Thr missense_variant 10/101 NM_016361.5 P1Q9NPH0-1
ACP6ENST00000613673.4 linkuse as main transcriptn.4487T>C non_coding_transcript_exon_variant 8/81
ACP6ENST00000609196.5 linkuse as main transcriptc.460+2698T>C intron_variant 3
ACP6ENST00000460583.1 linkuse as main transcriptn.828T>C non_coding_transcript_exon_variant 3/32

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251170
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135746
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000581
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:
0.00000137
AC:
2
AN:
1461782
Hom.:
0
Cov.:
29
AF XY:
0.00000275
AC XY:
2
AN XY:
727194
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

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 16, 2022The c.1265T>C (p.M422T) alteration is located in exon 10 (coding exon 10) of the ACP6 gene. This alteration results from a T to C substitution at nucleotide position 1265, causing the methionine (M) at amino acid position 422 to be replaced by a threonine (T). 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
0.062
BayesDel_addAF
Benign
-0.51
T
BayesDel_noAF
Benign
-0.79
CADD
Benign
0.75
DANN
Benign
0.28
DEOGEN2
Benign
0.054
T
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.052
N
LIST_S2
Benign
0.29
T
M_CAP
Benign
0.0035
T
MetaRNN
Benign
0.065
T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
1.7
L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.34
T
Sift4G
Benign
0.75
T
Polyphen
0.0
B
Vest4
0.059
MutPred
0.30
Gain of glycosylation at M422 (P = 0.0384);
MVP
0.048
ClinPred
0.026
T
GERP RS
1.9
Varity_R
0.12
gMVP
0.33

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: rs781853603; hg19: chr1-147119247; COSMIC: COSV65078032; COSMIC: COSV65078032; API