Genetic Variant NM_001099733.2:c.70A>T (chr18-905456-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001099733.2(ADCYAP1):c.70A>T(p.Ser24Cys) 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 1,458,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. S24R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ADCYAP1
NM_001099733.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.35

Publications

0 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.058039248).

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.70A>T	p.Ser24Cys	missense	Exon 2 of 5	NP_001093203.1	P18509
	ADCYAP1	NM_001117.5		c.70A>T	p.Ser24Cys	missense	Exon 1 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.70A>T	p.Ser24Cys	missense	Exon 2 of 5	ENSP00000411658.3	P18509
ADCYAP1	ENST00000579794.1	TSL:1	c.70A>T	p.Ser24Cys	missense	Exon 1 of 4	ENSP00000462647.1	P18509
ADCYAP1	ENST00000961508.1		c.70A>T	p.Ser24Cys	missense	Exon 1 of 3	ENSP00000631567.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1458970

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725912

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

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:

50554

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111978

Other (OTH)

AF:

0.00

AC:

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

0.039

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.17

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.53

M_CAP

Benign

0.0031

MetaRNN

Benign

0.058

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.2

PhyloP100

1.4

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.14

REVEL

Benign

0.088

Sift

Pathogenic

0.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.33

MutPred

0.43

Loss of disorder (P = 0.0031)

MVP

0.42

MPC

0.56

ClinPred

0.19

GERP RS

2.6

PromoterAI

-0.013

Neutral

(source)

Varity_R

0.10

gMVP

0.31

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over