chr19-50790697-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_ModerateBS2_Supporting

The NM_033068.3(ACP4):c.215C>T(p.Thr72Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000024 in 1,207,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. T72T) has been classified as Benign.

Frequency

Genomes: 𝑓 0.000058 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

ACP4
NM_033068.3 missense, splice_region

Scores

Splicing: ADA: 0.0009835

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.250

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]

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 -3 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12590903).

BS2

High AC in GnomAd4 at 8 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.215C>T	p.Thr72Met	missense_variant, splice_region_variant	Exon 2 of 11	ENST00000270593.2	NP_149059.1
LOC105372439	XR_936026.3 link	n.435-982G>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.215C>T	p.Thr72Met	missense_variant, splice_region_variant	Exon 2 of 11	1	NM_033068.3	ENSP00000270593.1		Q9BZG2-1
SMIM47	ENST00000636757.1 link	c.-59-982G>A		intron_variant	Intron 2 of 4	5		ENSP00000489695.1		A0A1B0GTG8

Frequencies

GnomAD3 genomes

AF:

0.0000289

AC:

AN:

138294

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000522

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000314

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000138

AC:

AN:

145232

AF XY:

0.0000256

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000406

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:

0.000237

GnomAD4 exome

AF:

0.0000196

AC:

AN:

1068942

Hom.:

Cov.:

AF XY:

0.0000247

AC XY:

AN XY:

526418

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23582

American (AMR)

AF:

0.0000352

AC:

AN:

28384

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15738

East Asian (EAS)

AF:

0.00

AC:

AN:

14154

South Asian (SAS)

AF:

0.00

AC:

AN:

74988

European-Finnish (FIN)

AF:

0.00

AC:

AN:

24082

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3564

European-Non Finnish (NFE)

AF:

0.0000201

AC:

AN:

845182

Other (OTH)

AF:

0.0000764

AC:

AN:

39268

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000578

AC:

AN:

138406

Hom.:

Cov.:

AF XY:

0.000105

AC XY:

AN XY:

66882

show subpopulations

African (AFR)

AF:

0.000156

AC:

AN:

38380

American (AMR)

AF:

0.00

AC:

AN:

14128

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3296

East Asian (EAS)

AF:

0.00

AC:

AN:

3876

South Asian (SAS)

AF:

0.00

AC:

AN:

3722

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8276

Middle Eastern (MID)

AF:

0.00

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.0000314

AC:

AN:

63620

Other (OTH)

AF:

0.00

AC:

AN:

1972

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000264

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 06, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.215C>T (p.T72M) alteration is located in exon 2 (coding exon 2) of the ACPT gene. This alteration results from a C to T substitution at nucleotide position 215, causing the threonine (T) at amino acid position 72 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

Benign

0.086

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.089

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.72

M_CAP

Benign

0.012

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PhyloP100

0.25

PrimateAI

Benign

0.27

PROVEAN

Benign

0.10

REVEL

Benign

0.073

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.013

Polyphen

0.70

Vest4

0.12

MutPred

0.40

Loss of phosphorylation at T72 (P = 0.0431);

MVP

0.095

MPC

0.26

ClinPred

0.18

GERP RS

-5.3

PromoterAI

0.0037

Neutral

(source)

Varity_R

0.045

gMVP

0.30

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00098

dbscSNV1_RF

Benign

0.052

SpliceAI score (max)

0.010

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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chr19-50790697-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