chr2-271938-A-T

Position:

• chr2-271938-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004300.4(ACP1):​c.116A>T​(p.Asn39Ile) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 13/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ACP1 NM_004300.4 missense, splice_region
• Scores: Splicing: ADA: 0.2675
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.00

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACP1	NM_004300.4	c.116A>T	p.Asn39Ile	missense_variant, splice_region_variant	2/6	ENST00000272065.10	NP_004291.1
ACP1	NM_007099.4	c.116A>T	p.Asn39Ile	missense_variant, splice_region_variant	2/6		NP_009030.1
ACP1	NM_001040649.3	c.116A>T	p.Asn39Ile	missense_variant, splice_region_variant	2/3		NP_001035739.1
ACP1	NR_024080.2	n.134A>T		splice_region_variant, non_coding_transcript_exon_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACP1	ENST00000272065.10	c.116A>T	p.Asn39Ile	missense_variant, splice_region_variant	2/6	1	NM_004300.4	ENSP00000272065	P3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2023

The c.116A>T (p.N39I) alteration is located in exon 2 (coding exon 2) of the ACP1 gene. This alteration results from a A to T substitution at nucleotide position 116, causing the asparagine (N) at amino acid position 39 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	0.16
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.18	.;T;.;T;T
Eigen	Benign	0.077
Eigen_PC	Benign	0.013
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D;D;D;D;.
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.39	T;T;T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	0.60	N;N;N;.;.
MutationTaster	Benign	0.74	D;D;D;D;D
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-3.7	D;D;D;D;D
REVEL	Benign	0.14
Sift	Benign	0.076	T;T;T;T;T
Sift4G	Benign	0.066	T;T;T;D;T
Polyphen		0.62	P;P;.;.;.
Vest4		0.51
MutPred		0.56		Loss of disorder (P = 0.0511);Loss of disorder (P = 0.0511);Loss of disorder (P = 0.0511);Loss of disorder (P = 0.0511);Loss of disorder (P = 0.0511);
MVP		0.62
MPC		0.11
ClinPred		0.67	D
GERP RS		2.9
Varity_R		0.61
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.27
dbscSNV1_RF	Benign	0.54
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-271938;