Genetic Variant ACP1:p.Thr141Thr (chr2-277250-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_004300.4(ACP1):c.423G>A(p.Thr141Thr) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0200

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 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 VariationId is 711059.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004300.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACP1	NM_004300.4	MANE Select	c.423G>A	p.Thr141Thr	synonymous	Exon 6 of 6	NP_004291.1	P24666-1
ACP1	NM_007099.4		c.423G>A	p.Thr141Thr	synonymous	Exon 6 of 6	NP_009030.1	P24666-2
ACP1	NR_024080.2		n.470G>A		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACP1	ENST00000272065.10	TSL:1 MANE Select	c.423G>A	p.Thr141Thr	synonymous	Exon 6 of 6	ENSP00000272065.5	P24666-1
ACP1	ENST00000272067.11	TSL:1	c.423G>A	p.Thr141Thr	synonymous	Exon 6 of 6	ENSP00000272067.6	P24666-2
ACP1	ENST00000453390.5	TSL:1	n.*239G>A		non_coding_transcript_exon	Exon 7 of 7	ENSP00000411121.1	F2Z2Q9

Frequencies

GnomAD3 genomes

AF:

0.00476

AC:

725

AN:

152156

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00474

AC:

1190

AN:

251230

AF XY:

0.00472

show subpopulations

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 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.:

Cov.:

AF XY:

0.00396

AC XY:

2876

AN XY:

727012

show subpopulations

African (AFR)

AF:

0.000329

AC:

AN:

33462

American (AMR)

AF:

0.00132

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000580

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.0294

AC:

1569

AN:

53420

Middle Eastern (MID)

AF:

0.000185

AC:

AN:

5412

European-Non Finnish (NFE)

AF:

0.00373

AC:

4153

AN:

1111998

Other (OTH)

AF:

0.00322

AC:

194

AN:

60340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

323

646

969

1292

1615

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

154

308

462

616

770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00476

AC:

725

AN:

152274

Hom.:

Cov.:

AF XY:

0.00591

AC XY:

440

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.000649

AC:

AN:

41574

American (AMR)

AF:

0.000719

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0359

AC:

381

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00435

AC:

296

AN:

68008

Other (OTH)

AF:

0.00331

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

107

143

179

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00325

Hom.:

Bravo

AF:

0.00199

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

7.4

(source)

DANN

Benign

0.87

PhyloP100

-0.020

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over