rs1085307111

Variant names:

• chr19-50793784-C-T
• rs1085307111
• NM_033068.3:c.746C>T
• ACP4 p.Pro249Leu

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PM2 PP5_Moderate BP4

The NM_033068.3(ACP4):​c.746C>T​(p.Pro249Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ACP4 NM_033068.3 missense
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 2.27
• Publications: 2 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]

ACP4 Gene-Disease associations (from GenCC):

• amelogenesis imperfecta type 1

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000268375 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 19-50793784-C-T is Pathogenic according to our data. Variant chr19-50793784-C-T is described in ClinVar as Pathogenic. ClinVar VariationId is 375694.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.28686902). . Strength limited to SUPPORTING due to the PP5.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033068.3. 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
	ACP4	NM_033068.3	MANE Select	c.746C>T	p.Pro249Leu	missense	Exon 7 of 11	NP_149059.1	Q9BZG2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACP4	ENST00000270593.2	TSL:1 MANE Select	c.746C>T	p.Pro249Leu	missense	Exon 7 of 11	ENSP00000270593.1	Q9BZG2-1
	ENSG00000268375	ENST00000594114.1	TSL:3	n.-200G>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Amelogenesis imperfecta, type 1J (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.066	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	1.0	L
PhyloP100		2.3
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.23
Sift	Uncertain	0.029	D
Sift4G	Benign	0.61	T
Varity_R		0.058
gMVP		0.65
Mutation Taster		=28/72	disease causing (ClinVar)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1085307111;

hg19: chr19-51297041;