rs200397867

Variant names:

• chr20-24963952-C-G
• rs200397867
• NM_020531.3:c.1112G>C

Your query was ambiguous. Multiple possible variants found:

• chr20-24963952-C-G
• chr20-24963952-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_020531.3(APMAP):​c.1112G>C​(p.Gly371Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,890 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G371C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: APMAP NM_020531.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.93
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.879

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020531.3. 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
	APMAP	NM_020531.3	MANE Select	c.1112G>C	p.Gly371Ala	missense	Exon 9 of 9	NP_065392.1	Q9HDC9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APMAP	ENST00000217456.3	TSL:1 MANE Select	c.1112G>C	p.Gly371Ala	missense	Exon 9 of 9	ENSP00000217456.2	Q9HDC9-1
	APMAP	ENST00000932674.1		c.1244G>C	p.Gly415Ala	missense	Exon 11 of 11	ENSP00000602733.1
	APMAP	ENST00000881539.1		c.1154G>C	p.Gly385Ala	missense	Exon 10 of 10	ENSP00000551598.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461890 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000719 AC: 8 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.053	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Uncertain	0.48	D
MutationAssessor	Pathogenic	4.1	H
PhyloP100		5.9
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Uncertain	0.59
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.59
MutPred		0.75		Loss of sheet (P = 0.0817)
MVP		0.76
MPC		0.84
ClinPred		1.0	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.86
gMVP		0.95
Mutation Taster		=10/90	disease causing

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

Other links and lift over

dbSNP: rs200397867; hg19: chr20-24944588; COSMIC: COSV105096086; COSMIC: COSV105096086;