19-50790783-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP5BP4

The NM_033068.3(ACP4):​c.226C>T​(p.Arg76Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000181 in 1,547,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

ACP4
NM_033068.3 missense

Scores

1
6
12

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 2.19
Variant links:
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)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 19-50790783-C-T is Pathogenic according to our data. Variant chr19-50790783-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 374864.Status of the report is no_assertion_criteria_provided, 0 stars.
BP4
Computational evidence support a benign effect (MetaRNN=0.35311794). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ACP4NM_033068.3 linkuse as main transcriptc.226C>T p.Arg76Cys missense_variant 3/11 ENST00000270593.2 NP_149059.1
LOC105372439XR_936026.3 linkuse as main transcriptn.435-1068G>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ACP4ENST00000270593.2 linkuse as main transcriptc.226C>T p.Arg76Cys missense_variant 3/111 NM_033068.3 ENSP00000270593.1 Q9BZG2-1
SMIM47ENST00000636757.1 linkuse as main transcriptc.-59-1068G>A intron_variant 5 ENSP00000489695.1 A0A1B0GTG8

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152136
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000579
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000199
AC:
3
AN:
151094
Hom.:
0
AF XY:
0.0000249
AC XY:
2
AN XY:
80292
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000269
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000165
AC:
23
AN:
1395650
Hom.:
0
Cov.:
35
AF XY:
0.0000145
AC XY:
10
AN XY:
688320
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000560
Gnomad4 SAS exome
AF:
0.0000126
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000158
Gnomad4 OTH exome
AF:
0.0000519
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152136
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74308
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000579
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000361
Hom.:
0
Bravo
AF:
0.0000151
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Amelogenesis imperfecta, type 1J Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMAug 15, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.33
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.33
T
Eigen
Uncertain
0.51
Eigen_PC
Uncertain
0.47
FATHMM_MKL
Benign
0.19
N
LIST_S2
Benign
0.74
T
M_CAP
Benign
0.032
D
MetaRNN
Benign
0.35
T
MetaSVM
Benign
-0.90
T
MutationAssessor
Pathogenic
3.2
M
PrimateAI
Benign
0.33
T
PROVEAN
Uncertain
-4.2
D
REVEL
Benign
0.24
Sift
Uncertain
0.0070
D
Sift4G
Uncertain
0.026
D
Polyphen
1.0
D
Vest4
0.34
MVP
0.17
MPC
0.60
ClinPred
0.89
D
GERP RS
4.7
Varity_R
0.19
gMVP
0.56

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1057519277; hg19: chr19-51294040; API