2-264985-G-T

Variant names:

• chr2-264985-G-T
• rs11691572
• NM_004300.4:c.21G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0053 (10 hom., cov: 33)
  • Exomes 𝑓: 0.00053 (6 hom.)
• Consequence: ACP1 NM_004300.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.52
• Publications: 5 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 10 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACP1	NM_004300.4	MANE Select	c.21G>T	p.Lys7Asn	missense	Exon 1 of 6	NP_004291.1
	ACP1	NM_007099.4		c.21G>T	p.Lys7Asn	missense	Exon 1 of 6	NP_009030.1
	ACP1	NM_001040649.3		c.21G>T	p.Lys7Asn	missense	Exon 1 of 3	NP_001035739.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACP1	ENST00000272065.10	TSL:1 MANE Select	c.21G>T	p.Lys7Asn	missense	Exon 1 of 6	ENSP00000272065.5
	ACP1	ENST00000272067.11	TSL:1	c.21G>T	p.Lys7Asn	missense	Exon 1 of 6	ENSP00000272067.6
	ACP1	ENST00000407983.7	TSL:1	c.21G>T	p.Lys7Asn	missense	Exon 1 of 3	ENSP00000385404.3

Frequencies

GnomAD3 genomes AF: 0.00522 AC: 795 AN: 152230 Hom.: 8 Cov.: 33

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

GnomAD2 exomes AF: 0.00123 AC: 305 AN: 248940 AF XY: 0.000979

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 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.: 6 Cov.: 31 AF XY: 0.000477 AC XY: 347 AN XY: 726752

African (AFR) AF: 0.0185 AC: 616 AN: 33278

American (AMR) AF: 0.000784 AC: 35 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26078

East Asian (EAS) AF: 0.00 AC: 0 AN: 39596

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86124

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.000521 AC: 3 AN: 5756

European-Non Finnish (NFE) AF: 0.0000207 AC: 23 AN: 1111596

Other (OTH) AF: 0.00151 AC: 91 AN: 60346

GnomAD4 genome AF: 0.00532 AC: 811 AN: 152346 Hom.: 10 Cov.: 33 AF XY: 0.00532 AC XY: 396 AN XY: 74490

African (AFR) AF: 0.0186 AC: 773 AN: 41588

American (AMR) AF: 0.00124 AC: 19 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68034

Other (OTH) AF: 0.00425 AC: 9 AN: 2116

Alfa AF: 0.00176 Hom.: 7

Bravo AF: 0.00567

ESP6500AA AF: 0.0168 AC: 74

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00150 AC: 182

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.34	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.83	T
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		1.5
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.083
Sift	Uncertain	0.022	D
Sift4G	Benign	0.089	T
Polyphen		0.0070	B
Vest4		0.37
MutPred		0.20		Loss of methylation at K7 (P = 0.0065)
MVP		0.63
MPC		0.057
ClinPred		0.073	T
GERP RS		3.3
PromoterAI		-0.010	Neutral
Varity_R		0.63
gMVP		0.43
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs11691572; hg19: chr2-264985;