19-50790784-GCCAGCAGCTGGAGCTGG-A

Variant names:

• chr19-50790784-GCCAGCAGCTGGAGCTGG-A
• NM_033068.3:c.227_244delGCCAGCAGCTGGAGCTGGinsA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP5_Moderate

The NM_033068.3(ACP4):​c.227_244delGCCAGCAGCTGGAGCTGGinsA​(p.Arg76GlnfsTer29) variant causes a frameshift, missense change. 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 (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ACP4 NM_033068.3 frameshift, missense
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 7.18
• Publications: 0 publications found

Genes affected

ACP4 (HGNC:14376): (acid phosphatase 4) Acid phosphatases are enzymes capable of hydrolyzing orthophosphoric acid esters in an acid medium. This gene is up-regulated by androgens and is down-regulated by estrogens in the prostate cancer cell line. This gene exhibits a lower level of expression in testicular cancer tissues than in normal tissues. The protein encoded by this gene has structural similarity to prostatic and lysosomal acid phosphatases. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

SMIM47 (HGNC:53452): (small integral membrane protein 47)

LOC105372439 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PP5: Variant 19-50790784-GCCAGCAGCTGGAGCTGG-A is Pathogenic according to our data. Variant chr19-50790784-GCCAGCAGCTGGAGCTGG-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1723827.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACP4	NM_033068.3	c.227_244delGCCAGCAGCTGGAGCTGGinsA	p.Arg76GlnfsTer29	frameshift_variant, missense_variant	Exon 3 of 11	ENST00000270593.2	NP_149059.1
LOC105372439	XR_936026.3	n.435-1086_435-1069delCCAGCTCCAGCTGCTGGCinsT		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACP4	ENST00000270593.2	c.227_244delGCCAGCAGCTGGAGCTGGinsA	p.Arg76GlnfsTer29	frameshift_variant, missense_variant	Exon 3 of 11	1	NM_033068.3	ENSP00000270593.1
SMIM47	ENST00000636757.1	c.-59-1086_-59-1069delCCAGCTCCAGCTGCTGGCinsT		intron_variant	Intron 2 of 4	5		ENSP00000489695.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Pathogenic:1

Dec 20, 2022

GeneDx

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene or region of a gene for which loss of function is not a well-established mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.2

Splicing

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

Other links and lift over

hg19: chr19-51294041;