Variant 20-24968960-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_020531.3(APMAP):c.973C>G(p.Pro325Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000178 in 1,461,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

APMAP
NM_020531.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.728

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]

APMAP links:

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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=0.17609152).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APMAP	NM_020531.3 linkuse as main transcript	c.973C>G	p.Pro325Ala	missense_variant	8/9	ENST00000217456.3	NP_065392.1	Q9HDC9-1
APMAP	XM_005260763.4 linkuse as main transcript	c.848+566C>G		intron_variant			XP_005260820.1	Q9HDC9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APMAP	ENST00000217456.3 linkuse as main transcript	c.973C>G	p.Pro325Ala	missense_variant	8/9	1	NM_020531.3	ENSP00000217456.2		Q9HDC9-1
APMAP	ENST00000451442.5 linkuse as main transcript	c.925C>G	p.Pro309Ala	missense_variant	8/10	5		ENSP00000395874.1		H0Y512

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251214

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135776

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:

0.0000440

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000178

AC:

AN:

1461738

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727174

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.0000216

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000247

AC:

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 submitter

clinical testing

Ambry Genetics

Nov 09, 2024

The c.973C>G (p.P325A) alteration is located in exon 8 (coding exon 8) of the APMAP gene. This alteration results from a C to G substitution at nucleotide position 973, causing the proline (P) at amino acid position 325 to be replaced by an alanine (A). 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

Benign

0.060

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.52

CADD

Benign

8.8

DANN

Benign

0.23

DEOGEN2

Benign

0.0071

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.80

M_CAP

Benign

0.0072

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.35

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.34

REVEL

Benign

0.21

Sift

Benign

0.98

Sift4G

Benign

0.78

Polyphen

0.0

Vest4

0.30

MutPred

0.81

Loss of disorder (P = 0.0969);

MVP

0.16

MPC

0.21

ClinPred

0.0075

GERP RS

-6.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.014

gMVP

0.43

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over