chr18-908302-A-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 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

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

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=0.34758157).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCYAP1	NM_001099733.2	c.280A>C	p.Lys94Gln	missense_variant	Exon 4 of 5	ENST00000450565.8	NP_001093203.1
ADCYAP1	NM_001117.5	c.280A>C	p.Lys94Gln	missense_variant	Exon 3 of 4		NP_001108.2
ADCYAP1	XM_005258081.5	c.697A>C	p.Lys233Gln	missense_variant	Exon 5 of 6		XP_005258138.2
ADCYAP1	XM_047437288.1	c.280A>C	p.Lys94Gln	missense_variant	Exon 4 of 5		XP_047293244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCYAP1	ENST00000450565.8	c.280A>C	p.Lys94Gln	missense_variant	Exon 4 of 5	1	NM_001099733.2	ENSP00000411658.3
ADCYAP1	ENST00000579794.1	c.280A>C	p.Lys94Gln	missense_variant	Exon 3 of 4	1		ENSP00000462647.1
ADCYAP1	ENST00000269200.5	n.278A>C		non_coding_transcript_exon_variant	Exon 2 of 3	2
ADCYAP1	ENST00000581602.1	n.271A>C		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 02, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.280A>C (p.K94Q) alteration is located in exon 4 (coding exon 3) of the ADCYAP1 gene. This alteration results from a A to C substitution at nucleotide position 280, causing the lysine (K) at amino acid position 94 to be replaced by a glutamine (Q). 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	0.12
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.40	T;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;T
MetaSVM	Benign	-0.32	T
MutationAssessor	Pathogenic	2.9	M;M
PrimateAI	Benign	0.42	T
REVEL	Benign	0.20
Sift4G	Uncertain	0.027	D;D
Polyphen		0.099	B;B
Vest4		0.27
MutPred		0.50		Gain of helix (P = 0.0128);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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-908303;