dbSNP rs554882864: ACP4:p.Thr72Arg (chr19-50790697-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_033068.3(ACP4):c.215C>G(p.Thr72Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000936 in 1,068,942 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T72M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 9.4e-7 ( 0 hom. )

Consequence

ACP4
NM_033068.3 missense, splice_region

Scores

Splicing: ADA: 0.0005374

Clinical Significance

Not reported in ClinVar

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.057728052).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACP4	NM_033068.3 link	c.215C>G	p.Thr72Arg	missense_variant, splice_region_variant	Exon 2 of 11	ENST00000270593.2	NP_149059.1
LOC105372439	XR_936026.3 link	n.435-982G>C		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>G	p.Thr72Arg	missense_variant, splice_region_variant	Exon 2 of 11	1	NM_033068.3	ENSP00000270593.1		Q9BZG2-1
SMIM47	ENST00000636757.1 link	c.-59-982G>C		intron_variant	Intron 2 of 4	5		ENSP00000489695.1		A0A1B0GTG8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000689

AC:

AN:

145232

AF XY:

0.00

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:

0.00

GnomAD4 exome

AF:

9.36e-7

AC:

AN:

1068942

Hom.:

Cov.:

AF XY:

0.00

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:

0.00

AC:

AN:

845182

Other (OTH)

AF:

0.00

AC:

AN:

39268

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.69

CADD

Benign

4.1

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.055

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0035

LIST_S2

Benign

0.11

M_CAP

Benign

0.0034

MetaRNN

Benign

0.058

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

PhyloP100

0.25

PrimateAI

Benign

0.27

PROVEAN

Benign

1.9

REVEL

Benign

0.047

Sift

Benign

0.26

Sift4G

Benign

0.29

Polyphen

0.0

Vest4

0.17

MutPred

0.48

Gain of MoRF binding (P = 0.0068);

MVP

0.040

MPC

0.13

ClinPred

0.11

GERP RS

-5.3

PromoterAI

-0.031

Neutral

(source)

Varity_R

0.072

gMVP

0.39

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00054

dbscSNV1_RF

Benign

0.0080

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over