rs878853218

Variant names:

• chr19-11575197-ATGAAATTCCCAGCCCCACT-A
• rs878853218
• NM_001611.5:c.772_790delAGTGGGGCTGGGAATTTCA

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1_Strong PP5_Very_Strong

The NM_001611.5(ACP5):​c.772_790delAGTGGGGCTGGGAATTTCA​(p.Ser258TrpfsTer39) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely pathogenic (★★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ACP5 NM_001611.5 frameshift
• Clinical Significance: Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:3
• Conservation: PhyloP100: 8.51
• Publications: 3 publications found

Genes affected

ACP5 (HGNC:124): (acid phosphatase 5, tartrate resistant) This gene encodes an iron containing glycoprotein which catalyzes the conversion of orthophosphoric monoester to alcohol and orthophosphate. It is the most basic of the acid phosphatases and is the only form not inhibited by L(+)-tartrate. [provided by RefSeq, Aug 2008]

ZNF627 (HGNC:30570): (zinc finger protein 627) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

LOC124904638 (HGNC:):

ACMG classification

Our verdict: Pathogenic. The variant received 12 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 5 pathogenic variants in the truncated region.
• PP5: Variant 19-11575197-ATGAAATTCCCAGCCCCACT-A is Pathogenic according to our data. Variant chr19-11575197-ATGAAATTCCCAGCCCCACT-A is described in ClinVar as Pathogenic/Likely_pathogenic. ClinVar VariationId is 225659.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001611.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACP5	NM_001611.5	MANE Select	c.772_790delAGTGGGGCTGGGAATTTCA	p.Ser258TrpfsTer39	frameshift	Exon 5 of 5	NP_001602.1
	ACP5	NM_001111034.3		c.772_790delAGTGGGGCTGGGAATTTCA	p.Ser258TrpfsTer39	frameshift	Exon 6 of 6	NP_001104504.1
	ACP5	NM_001111035.3		c.772_790delAGTGGGGCTGGGAATTTCA	p.Ser258TrpfsTer39	frameshift	Exon 7 of 7	NP_001104505.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACP5	ENST00000648477.1	MANE Select	c.772_790delAGTGGGGCTGGGAATTTCA	p.Ser258TrpfsTer39	frameshift	Exon 5 of 5	ENSP00000496973.1
	ACP5	ENST00000218758.10	TSL:1	c.772_790delAGTGGGGCTGGGAATTTCA	p.Ser258TrpfsTer39	frameshift	Exon 7 of 7	ENSP00000218758.4
	ACP5	ENST00000412435.7	TSL:2	c.772_790delAGTGGGGCTGGGAATTTCA	p.Ser258TrpfsTer39	frameshift	Exon 6 of 6	ENSP00000392374.1

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions as Germline

Significance: Pathogenic/Likely pathogenic

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
3	-	-	Spondyloenchondrodysplasia with immune dysregulation (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.5
Mutation Taster		=1/199	disease causing (ClinVar)

Splicing

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

Other links and lift over

dbSNP: rs878853218; hg19: chr19-11686012;