rs765029234

Variant names:

• chr18-905472-C-T
• rs765029234
• NM_001099733.2:c.86C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001099733.2(ADCYAP1):​c.86C>T​(p.Ala29Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ADCYAP1 NM_001099733.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.86
• Publications: 0 publications found

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]

ENSG00000265179 (HGNC:):

ACMG classification

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=0.14718819).

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.86C>T	p.Ala29Val	missense	Exon 2 of 5	NP_001093203.1	P18509
	ADCYAP1	NM_001117.5		c.86C>T	p.Ala29Val	missense	Exon 1 of 4	NP_001108.2	P18509

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCYAP1	ENST00000450565.8	TSL:1 MANE Select	c.86C>T	p.Ala29Val	missense	Exon 2 of 5	ENSP00000411658.3	P18509
	ADCYAP1	ENST00000579794.1	TSL:1	c.86C>T	p.Ala29Val	missense	Exon 1 of 4	ENSP00000462647.1	P18509
	ADCYAP1	ENST00000961508.1		c.86C>T	p.Ala29Val	missense	Exon 1 of 3	ENSP00000631567.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000405 AC: 1 AN: 247032 AF XY: 0.00000747

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: 0.0000559

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457034 Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0 AN XY: 725062

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48648

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111966

Other (OTH) AF: 0.00 AC: 0 AN: 60364

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T
Eigen	Benign	-0.20
Eigen_PC	Benign	0.0085
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		2.9
PrimateAI	Benign	0.38	T
REVEL	Benign	0.041
Sift4G	Benign	0.77	T
Polyphen		0.017	B
Vest4		0.27
MutPred		0.32		Loss of relative solvent accessibility (P = 0.0306)
MVP		0.76
MPC		0.59
ClinPred		0.24	T
GERP RS		4.1
PromoterAI		0.0042	Neutral
Varity_R		0.090
gMVP		0.45
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs765029234; hg19: chr18-905473;