19-50790783-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 1P and 2B. PP5BP4BS2_Supporting

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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R76H) has been classified as Uncertain significance.

Frequency

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

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

ACP4
NM_033068.3 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 2.19

Publications

2 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]

ACP4 links:

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

SMIM47 links:

LOC105372439 (HGNC:):

LOC105372439 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

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.

BS2

High AC in GnomAd4 at 5 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
ACP4	NM_033068.3 link	c.226C>T	p.Arg76Cys	missense_variant	Exon 3 of 11	ENST00000270593.2	NP_149059.1
LOC105372439	XR_936026.3 link	n.435-1068G>A		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACP4	ENST00000270593.2 link	c.226C>T	p.Arg76Cys	missense_variant	Exon 3 of 11	1	NM_033068.3	ENSP00000270593.1		Q9BZG2-1
SMIM47	ENST00000636757.1 link	c.-59-1068G>A		intron_variant	Intron 2 of 4	5		ENSP00000489695.1		A0A1B0GTG8

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152136

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.0000199

AC:

AN:

151094

AF XY:

0.0000249

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000165

AC:

AN:

1395650

Hom.:

Cov.:

AF XY:

0.0000145

AC XY:

AN XY:

688320

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31522

American (AMR)

AF:

0.00

AC:

AN:

35646

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25144

East Asian (EAS)

AF:

0.0000560

AC:

AN:

35726

South Asian (SAS)

AF:

0.0000126

AC:

AN:

79088

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48066

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4068

European-Non Finnish (NFE)

AF:

0.0000158

AC:

AN:

1078614

Other (OTH)

AF:

0.0000519

AC:

AN:

57776

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41428

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000579

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68006

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.565

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000361

Hom.:

Bravo

AF:

0.0000151

Asia WGS

AF:

0.000289

AC:

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

Aug 15, 2019

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.33

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.74

M_CAP

Benign

0.032

MetaRNN

Benign

0.35

MetaSVM

Benign

-0.90

MutationAssessor

Pathogenic

3.2

PhyloP100

2.2

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-4.2

REVEL

Benign

0.24

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.026

Polyphen

1.0

Vest4

0.34

MVP

0.17

MPC

0.60

ClinPred

0.89

GERP RS

4.7

PromoterAI

-0.020

Neutral

(source)

Varity_R

0.19

gMVP

0.56

Mutation Taster

=7/93

disease causing (ClinVar)

(source)

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

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19-50790783-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over