rs149799520

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001099733.2(ADCYAP1):​c.267C>A​(p.Asn89Lys) 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 1,460,524 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. N89N) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ADCYAP1
NM_001099733.2 missense

Scores

1
4
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.82
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.803

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ADCYAP1NM_001099733.2 linkc.267C>A p.Asn89Lys missense_variant Exon 4 of 5 ENST00000450565.8 NP_001093203.1 P18509
ADCYAP1NM_001117.5 linkc.267C>A p.Asn89Lys missense_variant Exon 3 of 4 NP_001108.2 P18509
ADCYAP1XM_005258081.5 linkc.684C>A p.Asn228Lys missense_variant Exon 5 of 6 XP_005258138.2 B7Z222
ADCYAP1XM_047437288.1 linkc.267C>A p.Asn89Lys missense_variant Exon 4 of 5 XP_047293244.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ADCYAP1ENST00000450565.8 linkc.267C>A p.Asn89Lys missense_variant Exon 4 of 5 1 NM_001099733.2 ENSP00000411658.3 P18509
ADCYAP1ENST00000579794.1 linkc.267C>A p.Asn89Lys missense_variant Exon 3 of 4 1 ENSP00000462647.1 P18509
ADCYAP1ENST00000269200.5 linkn.265C>A non_coding_transcript_exon_variant Exon 2 of 3 2
ADCYAP1ENST00000581602.1 linkn.258C>A non_coding_transcript_exon_variant Exon 1 of 2 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460524
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
726558
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 25, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.267C>A (p.N89K) alteration is located in exon 4 (coding exon 3) of the ADCYAP1 gene. This alteration results from a C to A substitution at nucleotide position 267, causing the asparagine (N) at amino acid position 89 to be replaced by a lysine (K). 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
0.23
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.28
T;T
Eigen
Benign
-0.0081
Eigen_PC
Benign
-0.045
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Benign
0.72
.;T
M_CAP
Benign
0.021
T
MetaRNN
Pathogenic
0.80
D;D
MetaSVM
Benign
-0.77
T
MutationAssessor
Uncertain
2.6
M;M
PrimateAI
Benign
0.44
T
REVEL
Benign
0.11
Sift4G
Uncertain
0.050
T;T
Polyphen
0.85
P;P
Vest4
0.70
MutPred
0.62
Gain of MoRF binding (P = 0.0269);Gain of MoRF binding (P = 0.0269);
MVP
0.84
MPC
1.1
ClinPred
0.91
D
GERP RS
1.8
Varity_R
0.078
gMVP
0.51

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: chr18-908290; API