20-24968963-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_020531.3(APMAP):​c.970C>T​(p.Arg324Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

APMAP
NM_020531.3 missense

Scores

8
8
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.38
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 Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.91

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
APMAPNM_020531.3 linkuse as main transcriptc.970C>T p.Arg324Cys missense_variant 8/9 ENST00000217456.3 NP_065392.1 Q9HDC9-1
APMAPXM_005260763.4 linkuse as main transcriptc.848+563C>T intron_variant XP_005260820.1 Q9HDC9-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
APMAPENST00000217456.3 linkuse as main transcriptc.970C>T p.Arg324Cys missense_variant 8/91 NM_020531.3 ENSP00000217456.2 Q9HDC9-1
APMAPENST00000451442.5 linkuse as main transcriptc.922C>T p.Arg308Cys missense_variant 8/105 ENSP00000395874.1 H0Y512

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152092
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
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:
0.00000796
AC:
2
AN:
251234
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135788
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000616
AC:
9
AN:
1461740
Hom.:
0
Cov.:
31
AF XY:
0.0000110
AC XY:
8
AN XY:
727180
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:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152092
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74296
show subpopulations
Gnomad4 AFR
AF:
0.0000242
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
Bravo
AF:
0.00000756
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 GeneticsOct 20, 2024The c.970C>T (p.R324C) alteration is located in exon 8 (coding exon 8) of the APMAP gene. This alteration results from a C to T substitution at nucleotide position 970, causing the arginine (R) at amino acid position 324 to be replaced by a cysteine (C). 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
0.86
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Pathogenic
0.16
CADD
Pathogenic
33
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.36
T
Eigen
Pathogenic
0.74
Eigen_PC
Uncertain
0.62
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.97
D
M_CAP
Uncertain
0.12
D
MetaRNN
Pathogenic
0.91
D
MetaSVM
Benign
-0.41
T
MutationAssessor
Pathogenic
3.8
H
PrimateAI
Uncertain
0.54
T
PROVEAN
Pathogenic
-6.2
D
REVEL
Uncertain
0.41
Sift
Uncertain
0.0010
D
Sift4G
Pathogenic
0.0010
D
Polyphen
1.0
D
Vest4
0.95
MutPred
0.67
Loss of disorder (P = 0.0606);
MVP
0.68
MPC
0.96
ClinPred
0.99
D
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.46
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: rs751217644; hg19: chr20-24949599; API