2-277250-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_004300.4(ACP1):c.423G>A(p.Thr141=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00416 in 1,613,706 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0048 (7 hom., cov: 33)
  • Exomes 𝑓: 0.0041 (43 hom.)
• Consequence: ACP1 NM_004300.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0200

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 2-277250-G-A is Benign according to our data. Variant chr2-277250-G-A is described in ClinVar as [Benign]. Clinvar id is 711059.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACP1	NM_004300.4	c.423G>A	p.Thr141=	synonymous_variant	6/6	ENST00000272065.10
ACP1	NM_007099.4	c.423G>A	p.Thr141=	synonymous_variant	6/6
ACP1	NR_024080.2	n.470G>A		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACP1	ENST00000272065.10	c.423G>A	p.Thr141=	synonymous_variant	6/6	1	NM_004300.4	P3

Frequencies

GnomAD3 genomes AF: 0.00476 AC: 725 AN: 152156 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.000651

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0359

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00435

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00474 AC: 1190 AN: 251230 Hom.: 17 AF XY: 0.00472 AC XY: 641 AN XY: 135826

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.00107

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.0317

Gnomad NFE exome AF: 0.00385

Gnomad OTH exome AF: 0.00375

GnomAD4 exome AF: 0.00410 AC: 5993 AN: 1461432 Hom.: 43 Cov.: 31 AF XY: 0.00396 AC XY: 2876 AN XY: 727012

Gnomad4 AFR exome AF: 0.000329

Gnomad4 AMR exome AF: 0.00132

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.0294

Gnomad4 NFE exome AF: 0.00373

Gnomad4 OTH exome AF: 0.00322

GnomAD4 genome AF: 0.00476 AC: 725 AN: 152274 Hom.: 7 Cov.: 33 AF XY: 0.00591 AC XY: 440 AN XY: 74460

Gnomad4 AFR AF: 0.000649

Gnomad4 AMR AF: 0.000719

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0359

Gnomad4 NFE AF: 0.00435

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00325 Hom.: 1

Bravo AF: 0.00199

Asia WGS AF: 0.000577 AC: 3 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 15, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
Cadd	Benign	7.4
Dann	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.24		Position offset: -23

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

Publications

LitVar

Other links and lift over

dbSNP: rs55709515; hg19: chr2-277250;