dbSNP rs774534318: ADCYAP1:p.Pro59Gln (chr18-907724-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001099733.2(ADCYAP1):c.176C>A(p.Pro59Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000289 in 1,382,796 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P59R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

ADCYAP1
NM_001099733.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.25

Publications

1 publications found

Variant links:

Genes affected

ADCYAP1 (HGNC:241): (adenylate cyclase activating polypeptide 1) This gene encodes a secreted proprotein that is further processed into multiple mature peptides. These peptides stimulate adenylate cyclase and increase cyclic adenosine monophosphate (cAMP) levels, resulting in the transcriptional activation of target genes. The products of this gene are key mediators of neuroendocrine stress responses. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2013]

ADCYAP1 links:

ENSG00000265179 (HGNC:):

ENSG00000265179 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3287976).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099733.2. 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
	ADCYAP1	NM_001099733.2	MANE Select	c.176C>A	p.Pro59Gln	missense	Exon 3 of 5	NP_001093203.1	P18509
	ADCYAP1	NM_001117.5		c.176C>A	p.Pro59Gln	missense	Exon 2 of 4	NP_001108.2	P18509

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADCYAP1	ENST00000450565.8	TSL:1 MANE Select	c.176C>A	p.Pro59Gln	missense	Exon 3 of 5	ENSP00000411658.3	P18509
ADCYAP1	ENST00000579794.1	TSL:1	c.176C>A	p.Pro59Gln	missense	Exon 2 of 4	ENSP00000462647.1	P18509
ADCYAP1	ENST00000961508.1		c.176C>A	p.Pro59Gln	missense	Exon 2 of 3	ENSP00000631567.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

133618

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000289

AC:

AN:

1382796

Hom.:

Cov.:

AF XY:

0.00000293

AC XY:

AN XY:

683648

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29992

American (AMR)

AF:

0.00

AC:

AN:

34994

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24506

East Asian (EAS)

AF:

0.0000283

AC:

AN:

35388

South Asian (SAS)

AF:

0.0000127

AC:

AN:

79032

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36248

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5288

European-Non Finnish (NFE)

AF:

0.00000185

AC:

AN:

1079754

Other (OTH)

AF:

0.00

AC:

AN:

57594

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000914

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.26

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.71

M_CAP

Benign

0.025

MetaRNN

Benign

0.33

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.9

PhyloP100

2.3

PrimateAI

Benign

0.35

REVEL

Benign

0.089

Sift4G

Benign

0.52

Polyphen

0.99

Vest4

0.26

MutPred

0.20

Loss of glycosylation at P59 (P = 0.079)

MVP

0.81

MPC

1.4

ClinPred

0.61

GERP RS

3.6

Varity_R

0.037

gMVP

0.41

Mutation Taster

=95/5

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over