chr2-264987-C-T

Position:

chr2-264987-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_004300.4(ACP1):c.23C>T(p.Ser8Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,613,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ACP1
NM_004300.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.29

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]

ACP1 links:

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]

SH3YL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.886

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ACP1	NM_004300.4 linkuse as main transcript	c.23C>T	p.Ser8Phe	missense_variant	1/6	ENST00000272065.10
ACP1	NM_007099.4 linkuse as main transcript	c.23C>T	p.Ser8Phe	missense_variant	1/6
ACP1	NM_001040649.3 linkuse as main transcript	c.23C>T	p.Ser8Phe	missense_variant	1/3
ACP1	NR_024080.2 linkuse as main transcript	n.41C>T		non_coding_transcript_exon_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACP1	ENST00000272065.10 linkuse as main transcript	c.23C>T	p.Ser8Phe	missense_variant	1/6	1	NM_004300.4	P3	P24666-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152246

Hom.:

Cov.:

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249118

Hom.:

AF XY:

0.00000741

AC XY:

AN XY:

134890

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:

0.00000137

AC:

AN:

1460922

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726788

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.00

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.00000378

Asia WGS

AF:

0.000289

AC:

AN:

3478

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 submitter

clinical testing

Ambry Genetics

Feb 15, 2023

The c.23C>T (p.S8F) alteration is located in exon 1 (coding exon 1) of the ACP1 gene. This alteration results from a C to T substitution at nucleotide position 23, causing the serine (S) at amino acid position 8 to be replaced by a phenylalanine (F). 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

Pathogenic

0.89

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

0.040

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.43

.;T;.;T;T

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.87

LIST_S2

Pathogenic

0.98

D;D;D;D;.

M_CAP

Uncertain

0.11

MetaRNN

Pathogenic

0.89

D;D;D;D;D

MetaSVM

Benign

-0.44

MutationAssessor

Uncertain

2.3

M;M;M;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-3.7

D;D;D;D;D

REVEL

Uncertain

0.30

Sift

Uncertain

0.0060

D;D;D;D;D

Sift4G

Uncertain

0.016

D;D;D;D;D

Polyphen

0.89

P;P;.;.;.

Vest4

0.72

MutPred

0.61

Loss of disorder (P = 0.0349);Loss of disorder (P = 0.0349);Loss of disorder (P = 0.0349);Loss of disorder (P = 0.0349);Loss of disorder (P = 0.0349);

MVP

0.77

MPC

0.31

ClinPred

0.98

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.97

gMVP

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.25

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.25

Position offset: -3

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over