2-264985-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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. 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.52

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

Verdict is Benign. Variant got -14 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_single_submitter, 1 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 GnomAd at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACP1	NM_004300.4	c.21G>T	p.Lys7Asn	missense_variant	1/6	ENST00000272065.10
ACP1	NM_007099.4	c.21G>T	p.Lys7Asn	missense_variant	1/6
ACP1	NM_001040649.3	c.21G>T	p.Lys7Asn	missense_variant	1/3
ACP1	NR_024080.2	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	c.21G>T	p.Lys7Asn	missense_variant	1/6	1	NM_004300.4	P3

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

GnomAD3 exomes AF: 0.00123 AC: 305 AN: 248940 Hom.: 1 AF XY: 0.000979 AC XY: 132 AN XY: 134798

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

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.: 10 Cov.: 33 AF XY: 0.00532 AC XY: 396 AN XY: 74490

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.: 2

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

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

May 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

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
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.83	T;T;D;D;.
MetaRNN	Benign	0.013	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;L;L;.;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.63	T
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	T
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

Other links and lift over

dbSNP: rs11691572; hg19: chr2-264985;