chr2-264985-G-T

Position:

chr2-264985-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004300.4(ACP1):c.21G>T(p.Lys7Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00098 in 1,613,176 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0053 ( 10 hom., cov: 33)

Exomes 𝑓: 0.00053 ( 6 hom. )

Consequence

ACP1
NM_004300.4 missense

Scores

Clinical Significance

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

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]

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012526184).

BP6

Variant 2-264985-G-T is Benign according to our data. Variant chr2-264985-G-T is described in ClinVar as [Benign]. Clinvar id is 717141.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00532 (811/152346) while in subpopulation AFR AF= 0.0186 (773/41588). AF 95% confidence interval is 0.0175. There are 10 homozygotes in gnomad4. There are 396 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ACP1	NM_004300.4 linkuse as main transcript	c.21G>T	p.Lys7Asn	missense_variant	1/6	ENST00000272065.10
ACP1	NM_007099.4 linkuse as main transcript	c.21G>T	p.Lys7Asn	missense_variant	1/6
ACP1	NM_001040649.3 linkuse as main transcript	c.21G>T	p.Lys7Asn	missense_variant	1/3
ACP1	NR_024080.2 linkuse as main transcript	n.39G>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.21G>T	p.Lys7Asn	missense_variant	1/6	1	NM_004300.4	P3	P24666-1

Frequencies

GnomAD3 genomes

AF:

0.00522

AC:

795

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0183

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00123

AC:

305

AN:

248940

Hom.:

AF XY:

0.000979

AC XY:

132

AN XY:

134798

show subpopulations

Gnomad AFR exome

AF:

0.0171

Gnomad AMR exome

AF:

0.000671

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:

0.0000267

Gnomad OTH exome

AF:

0.000829

GnomAD4 exome

AF:

0.000527

AC:

770

AN:

1460830

Hom.:

Cov.:

AF XY:

0.000477

AC XY:

347

AN XY:

726752

show subpopulations

Gnomad4 AFR exome

AF:

0.0185

Gnomad4 AMR exome

AF:

0.000784

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:

0.0000207

Gnomad4 OTH exome

AF:

0.00151

GnomAD4 genome

AF:

0.00532

AC:

811

AN:

152346

Hom.:

Cov.:

AF XY:

0.00532

AC XY:

396

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0186

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.000765

Hom.:

Bravo

AF:

0.00567

ESP6500AA

AF:

0.0168

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00150

AC:

182

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 31, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.57

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.34

.;T;.;T;T

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.83

T;T;D;D;.

MetaRNN

Benign

0.013

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;L;L;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-3.1

D;D;D;D;D

REVEL

Benign

0.083

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

0.073

GERP RS

3.3

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.

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