chr20-24970215-T-C

Position:

• chr20-24970215-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_020531.3(APMAP):​c.695A>G​(p.Glu232Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: APMAP NM_020531.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.83

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

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, 0.895

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APMAP	NM_020531.3	c.695A>G	p.Glu232Gly	missense_variant	6/9	ENST00000217456.3	NP_065392.1
APMAP	XM_005260763.4	c.695A>G	p.Glu232Gly	missense_variant	6/8		XP_005260820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APMAP	ENST00000217456.3	c.695A>G	p.Glu232Gly	missense_variant	6/9	1	NM_020531.3	ENSP00000217456.2
APMAP	ENST00000451442.5	c.647A>G	p.Glu216Gly	missense_variant	6/10	5		ENSP00000395874.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 29, 2023

The c.695A>G (p.E232G) alteration is located in exon 6 (coding exon 6) of the APMAP gene. This alteration results from a A to G substitution at nucleotide position 695, causing the glutamic acid (E) at amino acid position 232 to be replaced by a glycine (G). 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	0.72
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.099	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Pathogenic	3.0	M
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-6.7	D
REVEL	Pathogenic	0.69
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.91
MutPred		0.70		Loss of stability (P = 0.0304);
MVP		0.69
MPC		0.85
ClinPred		0.99	D
GERP RS		5.8
Varity_R		0.91
gMVP		0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-24950851;