19-50790697-C-G

Variant names:

• chr19-50790697-C-G
• rs554882864
• NM_033068.3:c.215C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 4P and 4B. PM1 PM2 BP4_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

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)

LOC105372439 (HGNC:):

ACMG classification

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

• PM1: In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 4 uncertain in NM_033068.3
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057728052).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033068.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACP4	NM_033068.3	MANE Select	c.215C>G	p.Thr72Arg	missense splice_region	Exon 2 of 11	NP_149059.1	Q9BZG2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACP4	ENST00000270593.2	TSL:1 MANE Select	c.215C>G	p.Thr72Arg	missense splice_region	Exon 2 of 11	ENSP00000270593.1	Q9BZG2-1
	SMIM47	ENST00000636757.1	TSL:5	c.-59-982G>C		intron	N/A	ENSP00000489695.1	A0A1B0GTG8

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000689 AC: 1 AN: 145232 AF XY: 0.00

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: 1 AN: 1068942 Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0 AN XY: 526418

African (AFR) AF: 0.00 AC: 0 AN: 23582

American (AMR) AF: 0.0000352 AC: 1 AN: 28384

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15738

East Asian (EAS) AF: 0.00 AC: 0 AN: 14154

South Asian (SAS) AF: 0.00 AC: 0 AN: 74988

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24082

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3564

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 845182

Other (OTH) AF: 0.00 AC: 0 AN: 39268

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	4.1
DANN	Benign	0.78
DEOGEN2	Benign	0.055	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0035	N
LIST_S2	Benign	0.11	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.25
PrimateAI	Benign	0.27	T
PROVEAN	Benign	1.9	N
REVEL	Benign	0.047
Sift	Benign	0.26	T
Sift4G	Benign	0.29	T
Polyphen		0.0	B
Vest4		0.17
MutPred		0.48		Gain of MoRF binding (P = 0.0068)
MVP		0.040
MPC		0.13
ClinPred		0.11	T
GERP RS		-5.3
PromoterAI		-0.031	Neutral
Varity_R		0.072
gMVP		0.39
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs554882864; hg19: chr19-51293954;