18-907724-C-A

Variant names:

• chr18-907724-C-A
• rs774534318
• NM_001099733.2:c.176C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: ADCYAP1 NM_001099733.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.25

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]

ENSG00000265671 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3287976).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCYAP1	NM_001099733.2	c.176C>A	p.Pro59Gln	missense_variant	Exon 3 of 5	ENST00000450565.8	NP_001093203.1
ADCYAP1	NM_001117.5	c.176C>A	p.Pro59Gln	missense_variant	Exon 2 of 4		NP_001108.2
ADCYAP1	XM_005258081.5	c.593C>A	p.Pro198Gln	missense_variant	Exon 4 of 6		XP_005258138.2
ADCYAP1	XM_047437288.1	c.176C>A	p.Pro59Gln	missense_variant	Exon 3 of 5		XP_047293244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCYAP1	ENST00000450565.8	c.176C>A	p.Pro59Gln	missense_variant	Exon 3 of 5	1	NM_001099733.2	ENSP00000411658.3
ADCYAP1	ENST00000579794.1	c.176C>A	p.Pro59Gln	missense_variant	Exon 2 of 4	1		ENSP00000462647.1
ADCYAP1	ENST00000269200.5	n.174C>A		non_coding_transcript_exon_variant	Exon 1 of 3	2
ENSG00000265671	ENST00000582554.1	n.-44G>T		upstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000289 AC: 4 AN: 1382796 Hom.: 0 Cov.: 42 AF XY: 0.00000293 AC XY: 2 AN XY: 683648

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000283

Gnomad4 SAS exome AF: 0.0000127

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000185

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

Bravo AF: 0.00000378

ExAC AF: 0.00000914 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.26	T;T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.71	.;T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.9	L;L
PrimateAI	Benign	0.35	T
REVEL	Benign	0.089
Sift4G	Benign	0.52	T;T
Polyphen		0.99	D;D
Vest4		0.26
MutPred		0.20		Loss of glycosylation at P59 (P = 0.079);Loss of glycosylation at P59 (P = 0.079);
MVP		0.81
MPC		1.4
ClinPred		0.61	D
GERP RS		3.6
Varity_R		0.037
gMVP		0.41

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

LitVar

Other links and lift over

dbSNP: rs774534318; hg19: chr18-907725;