NM_001099733.2:c.280A>C

Variant names:

• chr18-908302-A-C
• rs753870869
• NM_001099733.2:c.280A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001099733.2(ADCYAP1):​c.280A>C​(p.Lys94Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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)
• Consequence: ADCYAP1 NM_001099733.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.53
• 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]

ACMG classification

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=0.34758157).

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.280A>C	p.Lys94Gln	missense	Exon 4 of 5	NP_001093203.1	P18509
	ADCYAP1	NM_001117.5		c.280A>C	p.Lys94Gln	missense	Exon 3 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.280A>C	p.Lys94Gln	missense	Exon 4 of 5	ENSP00000411658.3	P18509
	ADCYAP1	ENST00000579794.1	TSL:1	c.280A>C	p.Lys94Gln	missense	Exon 3 of 4	ENSP00000462647.1	P18509
	ADCYAP1	ENST00000961508.1		c.242+512A>C		intron	N/A	ENSP00000631567.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

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	0.12
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.40	T
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.32	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		5.5
PrimateAI	Benign	0.42	T
REVEL	Benign	0.20
Sift4G	Uncertain	0.027	D
Polyphen		0.099	B
Vest4		0.27
MutPred		0.50		Gain of helix (P = 0.0128)
MVP		0.88
MPC		0.93
ClinPred		0.90	D
GERP RS		4.0
Varity_R		0.19
gMVP		0.43

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: rs753870869; hg19: chr18-908303;