rs1180680808

Variant names:

• chr2-264987-C-A
• rs1180680808
• NM_004300.4:c.23C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-264987-C-A
• chr2-264987-C-T
• chr2-264987-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_004300.4(ACP1):​c.23C>A​(p.Ser8Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,460,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S8F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ACP1 NM_004300.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.29
• Publications: 0 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

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.23C>A	p.Ser8Tyr	missense	Exon 1 of 6	NP_004291.1	P24666-1
	ACP1	NM_007099.4		c.23C>A	p.Ser8Tyr	missense	Exon 1 of 6	NP_009030.1	P24666-2
	ACP1	NM_001040649.3		c.23C>A	p.Ser8Tyr	missense	Exon 1 of 3	NP_001035739.1	A0A140VK37

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACP1	ENST00000272065.10	TSL:1 MANE Select	c.23C>A	p.Ser8Tyr	missense	Exon 1 of 6	ENSP00000272065.5	P24666-1
	ACP1	ENST00000272067.11	TSL:1	c.23C>A	p.Ser8Tyr	missense	Exon 1 of 6	ENSP00000272067.6	P24666-2
	ACP1	ENST00000407983.7	TSL:1	c.23C>A	p.Ser8Tyr	missense	Exon 1 of 3	ENSP00000385404.3	P24666-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1460924 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726790

African (AFR) AF: 0.00 AC: 0 AN: 33298

American (AMR) AF: 0.00 AC: 0 AN: 44660

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39610

South Asian (SAS) AF: 0.00 AC: 0 AN: 86150

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111618

Other (OTH) AF: 0.00 AC: 0 AN: 60346

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	31
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.50	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Benign	-0.53	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		4.3
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.25
Sift	Uncertain	0.013	D
Sift4G	Benign	0.071	T
Polyphen		1.0	D
Vest4		0.72
MutPred		0.62		Loss of loop (P = 0.0374)
MVP		0.77
MPC		0.34
ClinPred		0.99	D
GERP RS		4.2
PromoterAI		0.070	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.97
gMVP		0.49
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.75		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.75		Position offset: -3

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

Other links and lift over

dbSNP: rs1180680808; hg19: chr2-264987; COSMIC: COSV55243920; COSMIC: COSV55243920;