Genetic Variant AGER:p.Pro293Arg (chr6-32182333-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001136.5(AGER):c.878C>G(p.Pro293Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign 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. P293L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

AGER
NM_001136.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0850

Publications

0 publications found

Variant links:

Genes affected

AGER (HGNC:320): (advanced glycosylation end-product specific receptor) The advanced glycosylation end product (AGE) receptor encoded by this gene is a member of the immunoglobulin superfamily of cell surface receptors. It is a multiligand receptor, and besides AGE, interacts with other molecules implicated in homeostasis, development, and inflammation, and certain diseases, such as diabetes and Alzheimer's disease. Many alternatively spliced transcript variants encoding different isoforms, as well as non-protein-coding variants, have been described for this gene (PMID:18089847). [provided by RefSeq, May 2011]

AGER links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10320625).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AGER	NM_001136.5	MANE Select	c.878C>G	p.Pro293Arg	missense	Exon 8 of 11	NP_001127.1	Q15109-1
AGER	NM_001206929.2		c.926C>G	p.Pro309Arg	missense	Exon 8 of 11	NP_001193858.1	Q15109-6
AGER	NM_001206932.2		c.836C>G	p.Pro279Arg	missense	Exon 8 of 11	NP_001193861.1	Q15109-7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AGER	ENST00000375076.9	TSL:1 MANE Select	c.878C>G	p.Pro293Arg	missense	Exon 8 of 11	ENSP00000364217.4	Q15109-1
AGER	ENST00000375069.7	TSL:1	c.926C>G	p.Pro309Arg	missense	Exon 8 of 11	ENSP00000364210.4	Q15109-6
AGER	ENST00000438221.6	TSL:1	c.926C>G	p.Pro309Arg	missense	Exon 8 of 10	ENSP00000387887.2	Q15109-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460072

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726346

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52128

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111512

Other (OTH)

AF:

0.00

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.020

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.73

M_CAP

Benign

0.011

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.40

PhyloP100

-0.085

PrimateAI

Benign

0.30

PROVEAN

Benign

1.1

REVEL

Benign

0.075

Sift

Benign

1.0

Sift4G

Uncertain

0.042

Polyphen

0.95

Vest4

0.23

MutPred

0.30

Loss of disorder (P = 0.0734)

MVP

0.59

MPC

0.49

ClinPred

0.27

GERP RS

2.9

Varity_R

0.12

gMVP

0.37

Mutation Taster

=81/19

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over