chr2-264985-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_004300.4(ACP1):ā€‹c.21G>Cā€‹(p.Lys7Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000021 ( 0 hom. )

Consequence

ACP1
NM_004300.4 missense

Scores

1
4
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.52
Variant links:
Genes affected
ACP1 (HGNC:122): (acid phosphatase 1) The product of this gene belongs to the phosphotyrosine protein phosphatase family of proteins. It functions as an acid phosphatase and a protein tyrosine phosphatase by hydrolyzing protein tyrosine phosphate to protein tyrosine and orthophosphate. This enzyme also hydrolyzes orthophosphoric monoesters to alcohol and orthophosphate. This gene is genetically polymorphic, and three common alleles segregating at the corresponding locus give rise to six phenotypes. Each allele appears to encode at least two electrophoretically different isozymes, Bf and Bs, which are produced in allele-specific ratios. Multiple alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Aug 2008]
SH3YL1 (HGNC:29546): (SH3 and SYLF domain containing 1) Enables phosphatase binding activity and phosphatidylinositol binding activity. Predicted to act upstream of or within phosphatidylinositol biosynthetic process and regulation of ruffle assembly. Located in ruffle membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.31008565).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ACP1NM_004300.4 linkc.21G>C p.Lys7Asn missense_variant Exon 1 of 6 ENST00000272065.10 NP_004291.1 P24666-1Q59EH3
ACP1NM_007099.4 linkc.21G>C p.Lys7Asn missense_variant Exon 1 of 6 NP_009030.1 P24666-2
ACP1NM_001040649.3 linkc.21G>C p.Lys7Asn missense_variant Exon 1 of 3 NP_001035739.1 A0A140VK37
ACP1NR_024080.2 linkn.39G>C non_coding_transcript_exon_variant Exon 1 of 7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ACP1ENST00000272065.10 linkc.21G>C p.Lys7Asn missense_variant Exon 1 of 6 1 NM_004300.4 ENSP00000272065.5 P24666-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000402
AC:
1
AN:
248940
Hom.:
0
AF XY:
0.00000742
AC XY:
1
AN XY:
134798
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000328
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1460832
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
726752
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.57
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
19
DANN
Benign
0.96
DEOGEN2
Benign
0.34
.;T;.;T;T
Eigen
Benign
-0.36
Eigen_PC
Benign
-0.26
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Benign
0.83
T;T;D;D;.
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.31
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.2
L;L;L;.;.
PrimateAI
Uncertain
0.63
T
PROVEAN
Uncertain
-3.1
D;D;D;D;D
REVEL
Benign
0.095
Sift
Uncertain
0.022
D;D;T;T;T
Sift4G
Benign
0.089
T;T;T;T;T
Polyphen
0.0070
B;B;.;.;.
Vest4
0.37
MutPred
0.20
Loss of methylation at K7 (P = 0.0065);Loss of methylation at K7 (P = 0.0065);Loss of methylation at K7 (P = 0.0065);Loss of methylation at K7 (P = 0.0065);Loss of methylation at K7 (P = 0.0065);
MVP
0.63
MPC
0.057
ClinPred
0.86
D
GERP RS
3.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.63
gMVP
0.43

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: rs11691572; hg19: chr2-264985; API