20-24971538-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_020531.3(APMAP):​c.460G>A​(p.Gly154Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000142 in 1,614,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

APMAP
NM_020531.3 missense

Scores

10
7
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.84
Variant links:
Genes affected
APMAP (HGNC:13238): (adipocyte plasma membrane associated protein) Enables arylesterase activity. Predicted to be involved in biosynthetic process. Located in cell surface and membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.981

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
APMAPNM_020531.3 linkc.460G>A p.Gly154Ser missense_variant 5/9 ENST00000217456.3 NP_065392.1 Q9HDC9-1
APMAPXM_005260763.4 linkc.460G>A p.Gly154Ser missense_variant 5/8 XP_005260820.1 Q9HDC9-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
APMAPENST00000217456.3 linkc.460G>A p.Gly154Ser missense_variant 5/91 NM_020531.3 ENSP00000217456.2 Q9HDC9-1
APMAPENST00000451442.5 linkc.412G>A p.Gly138Ser missense_variant 5/105 ENSP00000395874.1 H0Y512

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152196
Hom.:
0
Cov.:
33
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:
0.00
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
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251476
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135906
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000144
AC:
21
AN:
1461880
Hom.:
0
Cov.:
31
AF XY:
0.0000124
AC XY:
9
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000189
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152196
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74356
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000130
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsSep 28, 2022The c.460G>A (p.G154S) alteration is located in exon 5 (coding exon 5) of the APMAP gene. This alteration results from a G to A substitution at nucleotide position 460, causing the glycine (G) at amino acid position 154 to be replaced by a serine (S). 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
Pathogenic
0.71
BayesDel_addAF
Pathogenic
0.28
D
BayesDel_noAF
Pathogenic
0.22
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.31
T
Eigen
Uncertain
0.68
Eigen_PC
Pathogenic
0.68
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.94
D
M_CAP
Uncertain
0.087
D
MetaRNN
Pathogenic
0.98
D
MetaSVM
Uncertain
0.51
D
MutationAssessor
Pathogenic
3.8
H
PrimateAI
Uncertain
0.71
T
PROVEAN
Pathogenic
-5.3
D
REVEL
Uncertain
0.61
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.98
MutPred
0.89
Gain of phosphorylation at G154 (P = 0.0276);
MVP
0.71
MPC
0.80
ClinPred
1.0
D
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.89
gMVP
0.92

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: rs753353812; hg19: chr20-24952174; API