11-47248704-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001610.4(ACP2):​c.86G>C​(p.Arg29Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 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. R29Q) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Consequence

ACP2
NM_001610.4 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.35
Variant links:
Genes affected
ACP2 (HGNC:123): (acid phosphatase 2, lysosomal) The protein encoded by this gene belongs to the histidine acid phosphatase family, which hydrolyze orthophosphoric monoesters to alcohol and phosphate. This protein is localized to the lysosomal membrane, and is chemically and genetically distinct from the red cell acid phosphatase. Mice lacking this gene showed multiple defects, including bone structure alterations, lysosomal storage defects, and an increased tendency towards seizures. An enzymatically-inactive allele of this gene in mice showed severe growth retardation, hair-follicle abnormalities, and an ataxia-like phenotype. Alternatively spliced transcript variants have been found for this gene. A C-terminally extended isoform is also predicted to be produced by the use of an alternative in-frame translation termination codon via a stop codon readthrough mechanism. [provided by RefSeq, Oct 2017]
NR1H3 (HGNC:7966): (nuclear receptor subfamily 1 group H member 3) The protein encoded by this gene belongs to the NR1 subfamily of the nuclear receptor superfamily. The NR1 family members are key regulators of macrophage function, controlling transcriptional programs involved in lipid homeostasis and inflammation. This protein is highly expressed in visceral organs, including liver, kidney and intestine. It forms a heterodimer with retinoid X receptor (RXR), and regulates expression of target genes containing retinoid response elements. Studies in mice lacking this gene suggest that it may play an important role in the regulation of cholesterol homeostasis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.21851131).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ACP2NM_001610.4 linkuse as main transcriptc.86G>C p.Arg29Pro missense_variant 1/11 ENST00000672073.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ACP2ENST00000672073.1 linkuse as main transcriptc.86G>C p.Arg29Pro missense_variant 1/11 NM_001610.4 P1P11117-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
46
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.081
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.19
T;.;T;T;T
Eigen
Benign
-0.35
Eigen_PC
Benign
-0.14
FATHMM_MKL
Benign
0.18
N
LIST_S2
Benign
0.36
T;T;T;.;T
M_CAP
Benign
0.028
D
MetaRNN
Benign
0.22
T;T;T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.0
N;.;.;.;.
MutationTaster
Benign
1.0
P;P;P;P;P;P;P
PrimateAI
Benign
0.48
T
PROVEAN
Benign
-0.56
N;N;N;N;N
REVEL
Benign
0.073
Sift
Benign
0.040
D;D;D;T;T
Sift4G
Benign
0.24
T;T;D;.;T
Polyphen
0.12
B;B;B;.;.
Vest4
0.15
MutPred
0.48
Loss of MoRF binding (P = 0.0073);Loss of MoRF binding (P = 0.0073);Loss of MoRF binding (P = 0.0073);Loss of MoRF binding (P = 0.0073);Loss of MoRF binding (P = 0.0073);
MVP
0.44
MPC
0.54
ClinPred
0.72
D
GERP RS
5.7
Varity_R
0.22
gMVP
0.50

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2167079; hg19: chr11-47270255; API