chr19-50790517-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 1P and 1B. PP3BS2_Supporting

The NM_033068.3(ACP4):​c.103G>A​(p.Val35Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000711 in 1,546,798 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

ACP4
NM_033068.3 missense

Scores

5
7
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.54

Publications

0 publications found
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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.822
BS2
High AC in GnomAdExome4 at 7 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ACP4NM_033068.3 linkc.103G>A p.Val35Met missense_variant Exon 1 of 11 ENST00000270593.2 NP_149059.1
LOC105372439XR_936026.3 linkn.435-802C>T intron_variant Intron 2 of 3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ACP4ENST00000270593.2 linkc.103G>A p.Val35Met missense_variant Exon 1 of 11 1 NM_033068.3 ENSP00000270593.1 Q9BZG2-1
SMIM47ENST00000636757.1 linkc.-59-802C>T intron_variant Intron 2 of 4 5 ENSP00000489695.1 A0A1B0GTG8

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152114
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.00
AC:
0
AN:
146954
AF XY:
0.00
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS 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:
0.00000502
AC:
7
AN:
1394684
Hom.:
0
Cov.:
34
AF XY:
0.00000291
AC XY:
2
AN XY:
687854
show subpopulations
African (AFR)
AF:
0.0000315
AC:
1
AN:
31740
American (AMR)
AF:
0.00
AC:
0
AN:
35690
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
24998
East Asian (EAS)
AF:
0.0000278
AC:
1
AN:
35914
South Asian (SAS)
AF:
0.00
AC:
0
AN:
79200
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
45438
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5422
European-Non Finnish (NFE)
AF:
0.00000371
AC:
4
AN:
1078416
Other (OTH)
AF:
0.0000173
AC:
1
AN:
57866
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.511
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152114
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74302
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41420
American (AMR)
AF:
0.00
AC:
0
AN:
15282
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.000193
AC:
1
AN:
5186
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4824
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10620
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000441
AC:
3
AN:
67994
Other (OTH)
AF:
0.00
AC:
0
AN:
2088
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 23, 2023
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.103G>A (p.V35M) alteration is located in exon 1 (coding exon 1) of the ACPT gene. This alteration results from a G to A substitution at nucleotide position 103, causing the valine (V) at amino acid position 35 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.63
BayesDel_addAF
Pathogenic
0.21
D
BayesDel_noAF
Uncertain
0.070
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.24
T
Eigen
Uncertain
0.53
Eigen_PC
Uncertain
0.46
FATHMM_MKL
Benign
0.32
N
LIST_S2
Benign
0.74
T
M_CAP
Uncertain
0.27
D
MetaRNN
Pathogenic
0.82
D
MetaSVM
Benign
-0.77
T
MutationAssessor
Pathogenic
3.8
H
PhyloP100
2.5
PrimateAI
Pathogenic
0.87
D
PROVEAN
Benign
-1.9
N
REVEL
Benign
0.27
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.0030
D
Polyphen
1.0
D
Vest4
0.78
MVP
0.59
MPC
0.52
ClinPred
0.99
D
GERP RS
4.4
PromoterAI
-0.0042
Neutral
Varity_R
0.49
gMVP
0.76
Mutation Taster
=78/22
polymorphism

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

Publications

Other links and lift over

dbSNP: rs533438473; hg19: chr19-51293774; COSMIC: COSV54518044; COSMIC: COSV54518044; API